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{"work":{"id":17017726,"created_at":"2015-10-19T18:57:31.985-07:00","from_world_paper_id":143019604,"updated_at":"2024-11-16T11:29:41.026-08:00","_data":{"grobid_abstract":"This study is the first to investigate the anticancer effect of 6-dehydrogingerdione (DGE), an active constituent of dietary ginger, in human breast cancer MDA-MB-231 and MCF-7 cells. DGE exhibited effective cell growth inhibition by inducing cancer cells to undergo G2/M phase arrest and apoptosis. Blockade of cell cycle was associated with increased levels of p21, and reduced amounts of cyclin B1, cyclin A, Cdc2 and Cdc25C. DGE also enhanced the levels of inactivated phosphorylated Cdc2 and Cdc25C. DGE triggered the mitochondrial apoptotic pathway indicated by a change in Bax/Bcl-2 ratios, resulting in caspase-9 activation. We also found the generation of reactive oxygen species is a critical mediator in DGE-induced cell growth inhibition. DGE clearly increased the activation of apoptosis signal-regulating kinase 1 and c-Jun N-terminal kinase (JNK), but not extracellular signal-regulated kinase 1/2 (ERK1/2) and p38. In addition, antioxidants vitamin C and catalase significantly decreased DGE-mediated JNK activation and apoptosis. Moreover, blocking JNK by specific inhibitors suppressed DGE-triggered mitochondrial apoptotic pathway. Taken together, these findings suggest that a critical role for reactive oxygen species and JNK in DGE-mediated apoptosis of human breast cancer.","publication_date":"2010,,","publication_name":"Molecular Nutrition \u0026 Food Research","grobid_abstract_attachment_id":"42356905"},"document_type":"paper","pre_hit_view_count_baseline":null,"quality":"high","language":"en","title":"6-Dehydrogingerdione, an active constituent of dietary ginger, induces cell cycle arrest and apoptosis through reactive oxygen species/c-Jun N-terminal kinase pathways in human breast cancer cells","broadcastable":false,"draft":null,"has_indexable_attachment":true,"indexable":true}}["work"]; window.loswp.workCoauthors = [36562658]; window.loswp.locale = "en"; window.loswp.countryCode = "SG"; window.loswp.cwvAbTestBucket = ""; window.loswp.designVariant = "ds_vanilla"; window.loswp.fullPageMobileSutdModalVariant = "full_page_mobile_sutd_modal"; window.loswp.useOptimizedScribd4genScript = false; window.loginModal = {}; window.loginModal.appleClientId = 'edu.academia.applesignon'; window.userInChina = "false";</script><script defer="" src="https://accounts.google.com/gsi/client"></script><div class="ds-loswp-container"><div class="ds-work-card--grid-container"><div class="ds-work-card--container js-loswp-work-card"><div class="ds-work-card--cover"><div class="ds-work-cover--wrapper"><div class="ds-work-cover--container"><button class="ds-work-cover--clickable js-swp-download-button" data-signup-modal="{"location":"swp-splash-paper-cover","attachmentId":42356905,"attachmentType":"pdf"}"><img alt="First page of “6-Dehydrogingerdione, an active constituent of dietary ginger, induces cell cycle arrest and apoptosis through reactive oxygen species/c-Jun N-terminal kinase pathways in human breast cancer cells”" class="ds-work-cover--cover-thumbnail" src="https://0.academia-photos.com/attachment_thumbnails/42356905/mini_magick20190217-2186-q7iflv.png?1550462032" /><img alt="PDF Icon" class="ds-work-cover--file-icon" src="//a.academia-assets.com/images/single_work_splash/adobe_icon.svg" /><div class="ds-work-cover--hover-container"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">download</span><p>Download Free PDF</p></div><div class="ds-work-cover--ribbon-container">Download Free PDF</div><div class="ds-work-cover--ribbon-triangle"></div></button></div></div></div><div class="ds-work-card--work-information"><h1 class="ds-work-card--work-title">6-Dehydrogingerdione, an active constituent of dietary ginger, induces cell cycle arrest and apoptosis through reactive oxygen species/c-Jun N-terminal kinase pathways in human breast cancer cells</h1><div class="ds-work-card--work-authors ds-work-card--detail"><a class="ds-work-card--author js-wsj-grid-card-author ds2-5-body-md ds2-5-body-link" data-author-id="36562658" href="https://independent.academia.edu/ChihhsingHung"><img alt="Profile image of Chih-hsing Hung" class="ds-work-card--author-avatar" src="//a.academia-assets.com/images/s65_no_pic.png" />Chih-hsing Hung</a></div><div class="ds-work-card--detail"><p class="ds-work-card--detail ds2-5-body-sm">2010, Molecular Nutrition & Food Research</p><div class="ds-work-card--work-metadata"><div class="ds-work-card--work-metadata__stat"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">visibility</span><p class="ds2-5-body-sm" id="work-metadata-view-count">…</p></div><div class="ds-work-card--work-metadata__stat"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">description</span><p class="ds2-5-body-sm">11 pages</p></div><div class="ds-work-card--work-metadata__stat"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">link</span><p class="ds2-5-body-sm">1 file</p></div></div><script>(async () => { const workId = 17017726; const worksViewsPath = "/v0/works/views?subdomain_param=api&work_ids%5B%5D=17017726"; const getWorkViews = async (workId) => { const response = await fetch(worksViewsPath); if (!response.ok) { throw new Error('Failed to load work views'); } const data = await response.json(); return data.views[workId]; }; // Get the view count for the work - we send this immediately rather than waiting for // the DOM to load, so it can be available as soon as possible (but without holding up // the backend or other resource requests, because it's a bit expensive and not critical). const viewCount = await getWorkViews(workId); const updateViewCount = (viewCount) => { try { const viewCountNumber = parseInt(viewCount, 10); if (viewCountNumber === 0) { // Remove the whole views element if there are zero views. document.getElementById('work-metadata-view-count')?.parentNode?.remove(); return; } const commaizedViewCount = viewCountNumber.toLocaleString(); const viewCountBody = document.getElementById('work-metadata-view-count'); if (!viewCountBody) { throw new Error('Failed to find work views element'); } viewCountBody.textContent = `${commaizedViewCount} views`; } catch (error) { // Remove the whole views element if there was some issue parsing. document.getElementById('work-metadata-view-count')?.parentNode?.remove(); throw new Error(`Failed to parse view count: ${viewCount}`, error); } }; // If the DOM is still loading, wait for it to be ready before updating the view count. if (document.readyState === "loading") { document.addEventListener('DOMContentLoaded', () => { updateViewCount(viewCount); }); // Otherwise, just update it immediately. } else { updateViewCount(viewCount); } })();</script></div><p class="ds-work-card--work-abstract ds-work-card--detail ds2-5-body-md">This study is the first to investigate the anticancer effect of 6-dehydrogingerdione (DGE), an active constituent of dietary ginger, in human breast cancer MDA-MB-231 and MCF-7 cells. DGE exhibited effective cell growth inhibition by inducing cancer cells to undergo G2/M phase arrest and apoptosis. Blockade of cell cycle was associated with increased levels of p21, and reduced amounts of cyclin B1, cyclin A, Cdc2 and Cdc25C. DGE also enhanced the levels of inactivated phosphorylated Cdc2 and Cdc25C. DGE triggered the mitochondrial apoptotic pathway indicated by a change in Bax/Bcl-2 ratios, resulting in caspase-9 activation. We also found the generation of reactive oxygen species is a critical mediator in DGE-induced cell growth inhibition. DGE clearly increased the activation of apoptosis signal-regulating kinase 1 and c-Jun N-terminal kinase (JNK), but not extracellular signal-regulated kinase 1/2 (ERK1/2) and p38. In addition, antioxidants vitamin C and catalase significantly decreased DGE-mediated JNK activation and apoptosis. Moreover, blocking JNK by specific inhibitors suppressed DGE-triggered mitochondrial apoptotic pathway. Taken together, these findings suggest that a critical role for reactive oxygen species and JNK in DGE-mediated apoptosis of human breast cancer.</p><div class="ds-work-card--button-container"><button class="ds2-5-button js-swp-download-button" data-signup-modal="{"location":"continue-reading-button--work-card","attachmentId":42356905,"attachmentType":"pdf","workUrl":"https://www.academia.edu/17017726/6_Dehydrogingerdione_an_active_constituent_of_dietary_ginger_induces_cell_cycle_arrest_and_apoptosis_through_reactive_oxygen_species_c_Jun_N_terminal_kinase_pathways_in_human_breast_cancer_cells"}">See full PDF</button><button class="ds2-5-button ds2-5-button--secondary js-swp-download-button" data-signup-modal="{"location":"download-pdf-button--work-card","attachmentId":42356905,"attachmentType":"pdf","workUrl":"https://www.academia.edu/17017726/6_Dehydrogingerdione_an_active_constituent_of_dietary_ginger_induces_cell_cycle_arrest_and_apoptosis_through_reactive_oxygen_species_c_Jun_N_terminal_kinase_pathways_in_human_breast_cancer_cells"}"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">download</span>Download PDF</button></div><div class="ds-signup-banner-trigger-container"><div class="ds-signup-banner-trigger ds-signup-banner-trigger-control"></div></div><div class="ds-signup-banner ds-signup-banner-control"><div id="ds-signup-banner-close-button"><button class="ds2-5-button ds2-5-button--secondary ds2-5-button--inverse"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">close</span></button></div><div class="ds-signup-banner-ctas"><img src="//a.academia-assets.com/images/academia-logo-capital-white.svg" /><h4 class="ds2-5-heading-serif-sm">Sign up for access to the world's latest research</h4><button class="ds2-5-button ds2-5-button--inverse ds2-5-button--full-width js-swp-download-button" data-signup-modal="{"location":"signup-banner"}">Sign up for free<span class="material-symbols-outlined" style="font-size: 20px" translate="no">arrow_forward</span></button></div><div class="ds-signup-banner-divider"></div><div class="ds-signup-banner-reasons"><div class="ds-signup-banner-reasons-item"><span class="material-symbols-outlined" style="font-size: 24px" translate="no">check</span><span>Get notified about relevant papers</span></div><div class="ds-signup-banner-reasons-item"><span class="material-symbols-outlined" style="font-size: 24px" translate="no">check</span><span>Save papers to use in your research</span></div><div class="ds-signup-banner-reasons-item"><span class="material-symbols-outlined" style="font-size: 24px" translate="no">check</span><span>Join the discussion with peers</span></div><div class="ds-signup-banner-reasons-item"><span class="material-symbols-outlined" style="font-size: 24px" translate="no">check</span><span>Track your impact</span></div></div></div><script>(() => { // Set up signup banner show/hide behavior: // 1. 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In the present study, we demonstrate the activation of all the three (MAPK) family members [extracellular signal-regulated protein kinase (ERK), c-jun N-terminal kinase (JNK) and P38] in response to BITC treatment. Exposure of Capan-2 cells with varying concentrations of BITC for 24 h resulted in the phosphorylation (activation) of ERK at Thr202/Tyr204, JNK at Thr183/Tyr185 and P38 at Thr180/Tyr182, leading to the induction of apoptosis. Similar MAPK activation was also observed in MiaPaCa-2 cells in response to BITC treatment. However, normal human pancreatic ductal epithelial cells did not show the activation of MAPK's and remained unaffected by BITC treatment. To confirm the role of ERK, JNK and P38 in BITC-induced G 2 /M arrest and apoptosis, Capan-2 cells were pre-treated with MAPK-specific inhibitors or MAPK8-short hairpin RNA (shRNA) prior to BITC treatment. Significant protection from BITC-induced G 2 /M arrest was observed in the cells pre-treated with MAPK kinase (MEK-1) but not JNK or P38 inhibitors. On the other hand, BITC-induced apoptosis was almost completely abrogated in the cells pre-treated with MEK-1, JNK or P38 inhibitors. Similarly, MAPK8-shRNA also offered almost complete protection against BITC-induced G 2 /M arrest and apoptosis. Furthermore, we observed that BITC treatment leads to the generation of reactive oxygen species (ROS) in Capan-2 and MiaPaCa-2 cells, which in part was orchestrated by depletion of reduced glutathione (GSH) level. Blocking ROS generation with N-acetyl-L-cysteine (NAC) significantly prevented GSH depletion and activation of ERK and JNK but not P38. Further, NAC or tiron prevented G 2 /M arrest by blocking G 2 /M regulatory proteins and completely protected the cells from BITC-induced apoptosis. Taken together, our results suggest that BITC-mediated G 2 /M arrest is mediated through ERK activation, whereas apoptosis is via ERK, JNK and P38.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Benzyl isothiocyanate mediated generation of reactive oxygen species causes cell cycle arrest and induces apoptosis via activation of MAPK in human pancreatic cancer cells","attachmentId":49966764,"attachmentType":"pdf","work_url":"https://www.academia.edu/4270842/Benzyl_isothiocyanate_mediated_generation_of_reactive_oxygen_species_causes_cell_cycle_arrest_and_induces_apoptosis_via_activation_of_MAPK_in_human_pancreatic_cancer_cells","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/4270842/Benzyl_isothiocyanate_mediated_generation_of_reactive_oxygen_species_causes_cell_cycle_arrest_and_induces_apoptosis_via_activation_of_MAPK_in_human_pancreatic_cancer_cells"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="1" data-entity-id="12533157" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/12533157/Glutathione_disulfide_induces_apoptosis_in_U937_cells_by_a_redox_mediated_p38_mitogen_activated_protein_kinase_pathway">Glutathione disulfide induces apoptosis in U937 cells by a redox-mediated p38 mitogen-activated protein kinase pathway</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="31424567" href="https://uniroma2.academia.edu/GiuseppeFilomeni">Giuseppe Filomeni</a></div><p class="ds-related-work--metadata ds2-5-body-xs">The FASEB Journal, 2002</p><p class="ds-related-work--abstract ds2-5-body-sm">Changes in the intracellular reduced/oxidized glutathione ratio (GSH/GSSG) are crucial reductionoxidation (redox) events that trigger downstream proliferation or death responses. We investigated the molecular mechanisms underlying redox-mediated cell signaling upon an oxidative insult by treating U937 cells with exogenous nonpermeable GSSG. This treatment results in a significant decrease of exofacial cell membrane thiol groups and intracellular decrement of GSH content, owing to its engagement in the formation of mixed disulfides. Changes in thioredoxin redox state were also observed, and they may be related to the activation of upstream ASK1 and selective induction of downstream p38 mitogen-activated protein kinase (MAPK) pathway, detectable by phosphorylation of MKK3/6 and p38 MAPK. Moreover, an increase in reactive oxygen species production was detected, and cells were committed to apoptosis along the mitochondrial pathway, evidenced by Bcl-2 down-regulation, cytochome c release from mitochondria, caspase-9 cleavage, and caspase-3 activation. GSH ethyl ester, a precursor of GSH, by counteracting intracellular mixed disulfide formation, canceled both p38 MAPK activation and GSSG-mediated apoptosis via inhibition of thioredoxin oxidation and stabilization of thioredoxin/ASK1 complex, whereas, blockage of p38 MAPK by specific inhibitor SB 203580 allowed apoptosis at a very reduced extent. Results suggest that kinase cascade may serve as a primary transducer of cytoplasmic oxidative signals to the nucleus before apoptosis-inducing signals are activated.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Glutathione disulfide induces apoptosis in U937 cells by a redox-mediated p38 mitogen-activated protein kinase pathway","attachmentId":46109472,"attachmentType":"pdf","work_url":"https://www.academia.edu/12533157/Glutathione_disulfide_induces_apoptosis_in_U937_cells_by_a_redox_mediated_p38_mitogen_activated_protein_kinase_pathway","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/12533157/Glutathione_disulfide_induces_apoptosis_in_U937_cells_by_a_redox_mediated_p38_mitogen_activated_protein_kinase_pathway"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="2" data-entity-id="11867485" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/11867485/Reactive_oxygen_species_generation_and_mitochondrial_dysfunction_in_the_apoptotic_cell_death_of_human_myeloid_leukemia_HL_60_cells_by_a_dietary_compound_">Reactive oxygen species generation and mitochondrial dysfunction in the apoptotic cell death of human myeloid leukemia HL-60 cells by a dietary compound …</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="29313788" href="https://independent.academia.edu/ShashiBhushan34">Shashi Bhushan</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Apoptosis, 2007</p><p class="ds-related-work--abstract ds2-5-body-sm">Induction of apoptosis in cancer cells has become the major focus of anti-cancer therapeutics development. WithaferinA, a major chemical constituent of Withania somnifera, reportedly shows cytotoxicity in a variety of tumor cell lines while its molecular mechanisms of action are not fully understood. We observed that withaferinA primarily induces oxidative stress in human leukemia HL-60 cells and in several other cancer cell lines. The withanolide induced early ROS generation and mitochondrial membrane potential (Dw mt ) loss, which preceded release of cytochrome c, translocation of Bax to mitochondria and apoptosis inducing factor to cell nuclei. These events paralleled activation of caspases -9, -3 and PARP cleavage. WA also activated extrinsic pathway significantly as evidenced by time dependent increase in caspase-8 activity vis-à-vis TNFR-1 over expression. WA mediated decreased expression of Bid may be an important event for cross talk between intrinsic and extrinsic signaling. Furthermore, withaferinA inhibited DNA binding of NF-jB and caused nuclear cleavage of p65/Rel by activated caspase-3. N-acetyl-cysteine rescued all these events suggesting thereby a pro-oxidant effect of withaferinA. The results of our studies demonstrate that withaferinA induced early ROS generation and mitochondrial dysfunction in cancer cells trigger events responsible for mitochondrial -dependent and -independent apoptosis pathways.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Reactive oxygen species generation and mitochondrial dysfunction in the apoptotic cell death of human myeloid leukemia HL-60 cells by a dietary compound …","attachmentId":46476855,"attachmentType":"pdf","work_url":"https://www.academia.edu/11867485/Reactive_oxygen_species_generation_and_mitochondrial_dysfunction_in_the_apoptotic_cell_death_of_human_myeloid_leukemia_HL_60_cells_by_a_dietary_compound_","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/11867485/Reactive_oxygen_species_generation_and_mitochondrial_dysfunction_in_the_apoptotic_cell_death_of_human_myeloid_leukemia_HL_60_cells_by_a_dietary_compound_"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="3" data-entity-id="56185040" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/56185040/c_Jun_NH2_Terminal_Kinase_Signaling_Axis_Regulates_Diallyl_Trisulfide_Induced_Generation_of_Reactive_Oxygen_Species_and_Cell_Cycle_Arrest_in_Human_Prostate_Cancer_Cells">c-Jun NH2-Terminal Kinase Signaling Axis Regulates Diallyl Trisulfide-Induced Generation of Reactive Oxygen Species and Cell Cycle Arrest in Human Prostate Cancer Cells</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="35792520" href="https://independent.academia.edu/AnnaHermanantosiewicz">Anna Herman-antosiewicz</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Cancer Research, 2006</p><p class="ds-related-work--abstract ds2-5-body-sm">We have shown previously that generation of reactive oxygen species (ROS) is a critical event in G 2-M phase cell cycle arrest caused by diallyl trisulfide (DATS), which is a highly promising anticancer constituent of processed garlic. Using DU145 and PC-3 human prostate cancer cells as a model, we now report a novel mechanism involving c-Jun NH 2-terminal kinase (JNK) signaling axis, which is known for its role in regulation of cell survival and apoptosis, in DATS-induced ROS production. The DATS-induced ROS generation, G 2-M phase cell cycle arrest and degradation, and hyperphosphorylation of Cdc25C were significantly attenuated in the presence of EUK134, a combined mimetic of superoxide dismutase and catalase. Interestingly, the DATS-induced ROS generation and G 2-M phase cell cycle arrest were also inhibited significantly in the presence of desferrioxamine, an iron chelator, but this protection was not observed with iron-saturated desferrioxamine. DATS treatment caused a marked increase in the level of labile iron that was accompanied by degradation of light chain of iron storage protein ferritin. Interestingly, DATSmediated degradation of ferritin, increase in labile iron pool, ROS generation, and/or cell cycle arrest were significantly attenuated by ectopic expression of a catalytically inactive mutant of JNK kinase 2 and RNA interference of stressactivated protein kinase/extracellular signal-regulated kinase 1 (SEK1), upstream kinases in JNK signal transduction pathway. In conclusion, the present study provides experimental evidence to indicate existence of a novel pathway involving JNK signaling axis in regulation of DATS-induced ROS generation.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"c-Jun NH2-Terminal Kinase Signaling Axis Regulates Diallyl Trisulfide-Induced Generation of Reactive Oxygen Species and Cell Cycle Arrest in Human Prostate Cancer Cells","attachmentId":71696957,"attachmentType":"pdf","work_url":"https://www.academia.edu/56185040/c_Jun_NH2_Terminal_Kinase_Signaling_Axis_Regulates_Diallyl_Trisulfide_Induced_Generation_of_Reactive_Oxygen_Species_and_Cell_Cycle_Arrest_in_Human_Prostate_Cancer_Cells","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/56185040/c_Jun_NH2_Terminal_Kinase_Signaling_Axis_Regulates_Diallyl_Trisulfide_Induced_Generation_of_Reactive_Oxygen_Species_and_Cell_Cycle_Arrest_in_Human_Prostate_Cancer_Cells"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="4" data-entity-id="78866186" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/78866186/15_Deoxy_12_14_Prostaglandin_J2_Protects_against_Nitrosative_PC12_Cell_Death_through_Up_regulation_of_Intracellular_Glutathione_Synthesis">15-Deoxy- 12,14-Prostaglandin J2 Protects against Nitrosative PC12 Cell Death through Up-regulation of Intracellular Glutathione Synthesis</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="31841723" href="https://independent.academia.edu/LuShelly">Shelly Lu</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Journal of Biological Chemistry, 2004</p><p class="ds-related-work--abstract ds2-5-body-sm">Nitrosative stress with subsequent inflammatory cell death has been associated with many neurodegenerative disorders. Expression of inducible nitric-oxide synthase and production of nitric oxide (NO) have been frequently elevated in many inflammatory disorders. NO can rapidly react with superoxide anion, producing more reactive peroxynitrite. In the present study, exposure of rat pheochromocytoma (PC12) cells to the peroxynitrite donor 3-morpholinosydnonimine hydrochloride (SIN-1) induced apoptosis, which accompanied depletion of intracellular glutathione (GSH), c-Jun Nterminal kinase activation, mitochondrial membrane depolarization, the cleavage of poly(ADP-ribose)polymerase, and DNA fragmentation. During SIN-1-induced apoptotic cell death, expression of inducible cyclooxygenase (COX-2), and peroxisome proliferator-activated receptor-␥ (PPAR␥) was elevated. SIN-1 treatment resulted in elevated production of 15-deoxy-⌬ 12,14-prostaglandin J 2 (15d-PGJ 2), an endogenous PPAR␥ activator. Preincubation with 15d-PGJ 2 rendered PC12 cells resistant to nitrosative stress induced by SIN-1. 15d-PGJ 2 fortified an intracellular GSH pool through up-regulation of glutamylcysteine ligase, thereby preventing cells from SIN-1-induced GSH depletion. The above findings suggest that 15d-PGJ 2 may act as a survival mediator capable of augmenting cellular thiol antioxidant capacity through up-regulation of the intracellular GSH synthesis in response to the nitrosative insult.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"15-Deoxy- 12,14-Prostaglandin J2 Protects against Nitrosative PC12 Cell Death through Up-regulation of Intracellular Glutathione Synthesis","attachmentId":85759316,"attachmentType":"pdf","work_url":"https://www.academia.edu/78866186/15_Deoxy_12_14_Prostaglandin_J2_Protects_against_Nitrosative_PC12_Cell_Death_through_Up_regulation_of_Intracellular_Glutathione_Synthesis","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/78866186/15_Deoxy_12_14_Prostaglandin_J2_Protects_against_Nitrosative_PC12_Cell_Death_through_Up_regulation_of_Intracellular_Glutathione_Synthesis"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="5" data-entity-id="53398055" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/53398055/Activation_and_role_of_mitogen_activated_protein_kinases_in_deoxycholic_acid_induced_apoptosis">Activation and role of mitogen-activated protein kinases in deoxycholic acid-induced apoptosis</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="33651143" href="https://independent.academia.edu/JesseMartinez9">Jesse Martinez</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Carcinogenesis, 2001</p><p class="ds-related-work--abstract ds2-5-body-sm">The bile acid deoxycholic acid (DCA) is a known tumor that have an important role in the pathogenesis of colon cancer. promoter and it has been suggested that DCA-induced The mechanism by which DCA or other bile acids function apoptosis plays an important role in colon tumor developis not clear. However, increasing evidence suggests that they ment. In this study we have characterized the capacity of may exert their tumor promoting activity by affecting DCA to stimulate mitogen-activated protein kinase intracellular signaling and gene expression, which ultimately (MAPK) activity and examined the effect that MAPK alters cell death and proliferation. It has been reported that activity had on DCA-induced apoptosis. Analysis of MAPK exposure to DCA can lead to the induction of a variety of activity in DCA-treated HCT116 cells using phosphorylagrowth regulatory genes, including cyclooxygenase-2 (9) and tion-specific antibodies and in vitro kinase assays indicated GADD153 (10), as well as stimulate the activity of the AP-1 that both the extracellular signal-regulated kinase (ERK) and NF-κB transcription factors (11,12). In addition, bile acids and p38 MAPK (p38), but not the c-Jun N-terminal kinase can regulate the levels of several enzymes involved in their (JNK), were activated. Using pharmacological inhibitors we own biosynthesis, including Cyp7α and Cyp27 in cells of determined that only ERK could influence DCA cytotoxicity hepatic origin (13,14). The Cyp7α enzyme is regulated at the and that elevated ERK activity could suppress DCAlevel of transcription by a negative feedback loop in which induced apoptosis. This observation was confirmed bile acids suppress transcription from the Cyp7 gene by genetically. Suppressing ERK activity by overexpressing a interfering with an as yet unidentified transcription factor that dominant negative form of the ERK MAP kinase resulted binds to a bile acid-responsive element in the 5Ј promoter in increased sensitivity to DCA-induced apoptosis whereas region of the gene (15,16). Importantly, this regulation of Cyp7 elevated ERK activity artificially produced by overexpresmay involve protein kinase C (PKC) (16). This is consistent sion of the wild-type ERK kinase blunted DCA-induced with pervious studies suggesting that bile acids can influence apoptosis. Taken together, our results suggest that DCA the activity of these protein kinases and suggests that bile can stimulate pro-apoptotic and anti-apoptotic signaling acids may alter the activity of intracellular signaling pathways pathways and that sensitivity to DCA-induced apoptosis (17-19). can be modulated by the ERK MAP kinase. In a previous study we demonstrated that DCA could cause activation of AP-1 and that this required both PKC and mitogenactivated protein kinase (MAPK) activities (11). MAPKs Abbreviations: AOM, azoxymethane; DCA, deoxycholic acid; ERK, ally, we found that elevated ERK activity can actually suppress extracellular signal-regulated kinase; JNK, c-Jun N-terminal kinase; MAPK, DCA-induced apoptosis. This result can be explained by a mitogen-activated protein kinase; MEK, MAPK/ERK kinase; NGF, neuron growth factor; p38, p38 MAP kinase; PKC, protein kinase C.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Activation and role of mitogen-activated protein kinases in deoxycholic acid-induced apoptosis","attachmentId":70261762,"attachmentType":"pdf","work_url":"https://www.academia.edu/53398055/Activation_and_role_of_mitogen_activated_protein_kinases_in_deoxycholic_acid_induced_apoptosis","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/53398055/Activation_and_role_of_mitogen_activated_protein_kinases_in_deoxycholic_acid_induced_apoptosis"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="6" data-entity-id="20535688" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/20535688/Reactive_oxygen_species_and_c_Jun_N_terminal_kinases_contribute_to_TEMPO_induced_apoptosis_in_L5178Y_cells">Reactive oxygen species and c-Jun N-terminal kinases contribute to TEMPO-induced apoptosis in L5178Y cells</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="40831116" href="https://independent.academia.edu/MeiNan">Nan Mei</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Chemico-biological interactions, 2015</p><p class="ds-related-work--abstract ds2-5-body-sm">The biological consequences of exposure to piperidine nitroxides is a concern, given their widespread use in manufacturing processes and their potential use in clinical applications. Our previous study reported that TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl), a low molecular weight free radical, possesses pro-oxidative activity in L5178Y cells. In this study, we investigated and characterized the role of reactive oxygen species (ROS) in TEMPO-induced toxicity in L5178Y cells. We found that TEMPO induced time- and concentration-dependent intracellular ROS production and glutathione depletion. TEMPO also induced apoptosis as demonstrated by increased caspase-3/7 activity, an increased proportion of annexin V stained cells, and decreased expression of anti-apoptotic proteins including Bcl-2, Bcl-xL and Mcl-1. N-acetylcysteine, a ROS scavenger, attenuated the ROS production and apoptosis induced by TEMPO. Moreover, Western blot analyses revealed that TEMPO activated γ-H2A.X, a hallmar...</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Reactive oxygen species and c-Jun N-terminal kinases contribute to TEMPO-induced apoptosis in L5178Y cells","attachmentId":41424619,"attachmentType":"pdf","work_url":"https://www.academia.edu/20535688/Reactive_oxygen_species_and_c_Jun_N_terminal_kinases_contribute_to_TEMPO_induced_apoptosis_in_L5178Y_cells","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/20535688/Reactive_oxygen_species_and_c_Jun_N_terminal_kinases_contribute_to_TEMPO_induced_apoptosis_in_L5178Y_cells"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="7" data-entity-id="12533137" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/12533137/Activation_of_c_Jun_N_terminal_kinase_is_required_for_apoptosis_triggered_by_glutathione_disulfide_in_neuroblastoma_cells">Activation of c-Jun-N-terminal kinase is required for apoptosis triggered by glutathione disulfide in neuroblastoma cells</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="31424567" href="https://uniroma2.academia.edu/GiuseppeFilomeni">Giuseppe Filomeni</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Free Radical Biology and Medicine, 2005</p><p class="ds-related-work--abstract ds2-5-body-sm">Changes in intracellular redox status are crucial events that trigger downstream proliferation or death responses through activation of specific signaling pathways. Moreover, cell responses to oxidative challenge may depend on the pattern of redox-sensitive molecular factors. The stress-activated protein kinases c-Jun-N-terminal kinase (JNK) and p38 MAP kinase (p38 MAPK ) are implicated in different forms of apoptotic neuronal cell death. Here, we investigated the effects, on neuroblastoma cells, of the prooxidant molecule GSSG, which we previously demonstrated to be an efficient proapoptotic compound able to activate the p38 MAPK death pathway in promonocytic cells. We found that neuroblastoma cells are not prone to GSSG-induced apoptosis, although the treatment slightly induced growth arrest through the accumulation of p53 and its downstream target gene, p21. However, GSSG treatment became cytotoxic when cells were previously depleted of intracellular GSH content. Under this condition, apoptosis was triggered by an increased production of superoxide that led to a specific activation of the JNK-dependent pathway. The involvement of superoxide and JNK was demonstrated by cell death inhibition in experiments carried out in the presence of Cu,Zn superoxide dismutase or with specific inhibitors of JNK activity. Our data give support to the studies that indicate preferential requirements for the involvement of stress-activated kinases in apoptotic neuronal cells.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Activation of c-Jun-N-terminal kinase is required for apoptosis triggered by glutathione disulfide in neuroblastoma cells","attachmentId":46109526,"attachmentType":"pdf","work_url":"https://www.academia.edu/12533137/Activation_of_c_Jun_N_terminal_kinase_is_required_for_apoptosis_triggered_by_glutathione_disulfide_in_neuroblastoma_cells","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/12533137/Activation_of_c_Jun_N_terminal_kinase_is_required_for_apoptosis_triggered_by_glutathione_disulfide_in_neuroblastoma_cells"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="8" data-entity-id="19390331" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/19390331/Flavonoid_induced_glutathione_depletion_Potential_implications_for_cancer_treatment">Flavonoid-induced glutathione depletion: Potential implications for cancer treatment</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="39586461" href="https://independent.academia.edu/RemyKachadourian">Remy Kachadourian</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Free Radical Biology and Medicine, 2006</p><p class="ds-related-work--abstract ds2-5-body-sm">Hydroxychalcones are naturally occurring compounds that continue to attract considerable interest because of their anti-inflammatory and antiangiogenic properties. They have been reported to inhibit the synthesis of the inducible nitric oxide synthase and to induce the expression of heme oxygenase-1. This study examines the mechanisms by which 2′,5′-dihydroxychalcone (2′,5′-DHC) induces an increase in cellular glutathione (GSH) levels using a cell line stably expressing a luciferase reporter gene driven by antioxidant-response elements (MCF-7/AREc32). The 2′,5′-DHC-induced increase in cellular GSH levels was partially inhibited by the catalytic antioxidant MnTDE-1,3-IP 5+ , suggesting that reactive oxygen species (ROS) mediate the antioxidant adaptive response. 2′,5′-DHC treatment induced phosphorylation of the c-Jun N-terminal kinase (JNK) pathway, which was also inhibited by MnTDE-1,3-IP 5+ . These findings suggest a ROS-dependent activation of the AP-1 transcriptional response. However, whereas 2′,5′-DHC triggered the NF-E2-related factor 2 (Nrf2) transcriptional response, cotreatment with MnTDE-1,3-IP 5+ did not decrease 2′,5′-DHCinduced Nrf2/ARE activity, showing that this pathway is not dependent on ROS. Moreover, pharmacological inhibitors of mitogen-activated protein kinase (MAPK) pathways showed a role for JNK and p38MAPK in mediating the 2′,5′-DHC-induced Nrf2 response. These findings suggest that the 2′,5′-DHC-induced increase in GSH levels results from a combination of ROS-dependent and ROS-independent pathways.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Flavonoid-induced glutathione depletion: Potential implications for cancer treatment","attachmentId":40593939,"attachmentType":"pdf","work_url":"https://www.academia.edu/19390331/Flavonoid_induced_glutathione_depletion_Potential_implications_for_cancer_treatment","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/19390331/Flavonoid_induced_glutathione_depletion_Potential_implications_for_cancer_treatment"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="9" data-entity-id="26625722" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/26625722/Antiapoptotic_effects_of_dietary_antioxidants_towards_N_nitrosopiperidine_and_N_nitrosodibutylamine_induced_apoptosis_in_HL_60_and_HepG2_cells">Antiapoptotic effects of dietary antioxidants towards N -nitrosopiperidine and N -nitrosodibutylamine-induced apoptosis in HL-60 and HepG2 cells</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="33275760" href="https://independent.academia.edu/AHaza">Ana Haza</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Journal of Applied Toxicology, 2009</p><p class="ds-related-work--abstract ds2-5-body-sm">The aim of this work was to determine the effect of vitamin C, diallyl disulfide (DADS) and dipropyl disulfide (DPDS) towards N-nitrosopiperidine (NPIP) and N-nitrosodibutylamine (NDBA)-induced apoptosis in human leukemia (HL-60) and hepatoma (HepG2) cell lines using the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Antiapoptotic effects of dietary antioxidants towards N -nitrosopiperidine and N -nitrosodibutylamine-induced apoptosis in HL-60 and HepG2 cells","attachmentId":46911168,"attachmentType":"pdf","work_url":"https://www.academia.edu/26625722/Antiapoptotic_effects_of_dietary_antioxidants_towards_N_nitrosopiperidine_and_N_nitrosodibutylamine_induced_apoptosis_in_HL_60_and_HepG2_cells","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/26625722/Antiapoptotic_effects_of_dietary_antioxidants_towards_N_nitrosopiperidine_and_N_nitrosodibutylamine_induced_apoptosis_in_HL_60_and_HepG2_cells"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div></div></div><div class="ds-sticky-ctas--wrapper js-loswp-sticky-ctas hidden"><div class="ds-sticky-ctas--grid-container"><div class="ds-sticky-ctas--container"><button class="ds2-5-button js-swp-download-button" data-signup-modal="{"location":"continue-reading-button--sticky-ctas","attachmentId":42356905,"attachmentType":"pdf","workUrl":null}">See full PDF</button><button class="ds2-5-button ds2-5-button--secondary js-swp-download-button" data-signup-modal="{"location":"download-pdf-button--sticky-ctas","attachmentId":42356905,"attachmentType":"pdf","workUrl":null}"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">download</span>Download PDF</button></div></div></div><div class="ds-below-fold--grid-container"><div class="ds-work--container js-loswp-embedded-document"><div class="attachment_preview" data-attachment="Attachment_42356905" style="display: none"><div class="js-scribd-document-container"><div class="scribd--document-loading js-scribd-document-loader" style="display: block;"><img alt="Loading..." src="//a.academia-assets.com/images/loaders/paper-load.gif" /><p>Loading Preview</p></div></div><div style="text-align: center;"><div class="scribd--no-preview-alert js-preview-unavailable"><p>Sorry, preview is currently unavailable. You can download the paper by clicking the button above.</p></div></div></div></div><div class="ds-sidebar--container js-work-sidebar"><div class="ds-related-content--container"><h2 class="ds-related-content--heading">Related papers</h2><div class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="0" data-entity-id="12533178" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/12533178/Reactive_oxygen_species_dependent_c_Jun_NH2_terminal_kinase_c_Jun_signaling_cascade_mediates_neuroblastoma_cell_death_induced_by_diallyl_disulfide">Reactive oxygen species-dependent c-Jun NH2-terminal kinase/c-Jun signaling cascade mediates neuroblastoma cell death induced by diallyl disulfide</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="31424567" href="https://uniroma2.academia.edu/GiuseppeFilomeni">Giuseppe Filomeni</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Cancer research, 2003</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Reactive oxygen species-dependent c-Jun NH2-terminal kinase/c-Jun signaling cascade mediates neuroblastoma cell death induced by diallyl disulfide","attachmentId":46109459,"attachmentType":"pdf","work_url":"https://www.academia.edu/12533178/Reactive_oxygen_species_dependent_c_Jun_NH2_terminal_kinase_c_Jun_signaling_cascade_mediates_neuroblastoma_cell_death_induced_by_diallyl_disulfide","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline 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class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="46240220" href="https://independent.academia.edu/KyuShikJeong">Kyu-Shik Jeong</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Chemico-Biological Interactions, 2001</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Apoptosis of PC12 cells by 4-hydroxy-2-nonenal is mediated through selective activation of the c-Jun N-Terminal protein kinase pathway","attachmentId":44324781,"attachmentType":"pdf","work_url":"https://www.academia.edu/23938886/Apoptosis_of_PC12_cells_by_4_hydroxy_2_nonenal_is_mediated_through_selective_activation_of_the_c_Jun_N_Terminal_protein_kinase_pathway","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free 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href="https://du-in.academia.edu/shashibhushan">shashi bhushan</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Apoptosis, 2007</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Reactive oxygen species generation and mitochondrial dysfunction in the apoptotic cell death of human myeloid leukemia HL60 cells by a dietary compound withaferin A with concomitant protection by N -acetyl cysteine","attachmentId":49299498,"attachmentType":"pdf","work_url":"https://www.academia.edu/5420396/Reactive_oxygen_species_generation_and_mitochondrial_dysfunction_in_the_apoptotic_cell_death_of_human_myeloid_leukemia_HL60_cells_by_a_dietary_compound_withaferin_A_with_concomitant_protection_by_N_acetyl_cysteine","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span 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href="https://www.academia.edu/13272628/Pharmacologic_inhibitors_of_extracellular_signal_regulated_kinase_ERKs_and_c_Jun_NH2_terminal_kinase_JNK_decrease_glutathione_content_and_sensitize_human_promonocytic_leukemia_Cells_to_arsenic_trioxide_induced_apoptosis">Pharmacologic inhibitors of extracellular signal-regulated kinase (ERKs) and c-Jun NH2-terminal kinase (JNK) decrease glutathione content and sensitize human promonocytic leukemia Cells to arsenic trioxide-induced apoptosis</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="32526625" href="https://uah.academia.edu/CarlosFernandez">Carlos Fernandez</a><span>, </span><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="36128903" href="https://csic.academia.edu/PatricioAller">Patricio Aller</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Journal of Cellular Physiology, 2006</p><div 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