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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.","publication_date":"2007,,","publication_name":"Apoptosis","grobid_abstract_attachment_id":"46476855"},"document_type":"paper","pre_hit_view_count_baseline":null,"quality":"high","language":"en","title":"Reactive oxygen species generation and mitochondrial dysfunction in the apoptotic cell death of human myeloid leukemia HL-60 cells by a dietary compound …","broadcastable":true,"draft":null,"has_indexable_attachment":true,"indexable":true}}["work"]; window.loswp.workCoauthors = [29313788]; 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; 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class="ds-related-content--container ds-top-related-works--container"><h2 class="ds-related-content--heading">Related papers</h2><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="0" data-entity-id="5420396" 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/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">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</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="7575940" href="https://du-in.academia.edu/shashibhushan">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 (Δψmt) 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-κB 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 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 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/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"><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="17042173" 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/17042173/Withaferin_A_induces_apoptosis_in_human_melanoma_cells_through_generation_of_reactive_oxygen_species_and_down_regulation_of_Bcl_2">Withaferin A induces apoptosis in human melanoma cells through generation of reactive oxygen species and down-regulation of Bcl-2</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="36681544" href="https://independent.academia.edu/CindyGallerne">Cindy Gallerne</a><span>, </span><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="36597955" href="https://independent.academia.edu/BrigitteDebuire">Brigitte Debuire</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Apoptosis, 2011</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":"Withaferin A induces apoptosis in human melanoma cells through generation of reactive oxygen species and down-regulation of Bcl-2","attachmentId":42348528,"attachmentType":"pdf","work_url":"https://www.academia.edu/17042173/Withaferin_A_induces_apoptosis_in_human_melanoma_cells_through_generation_of_reactive_oxygen_species_and_down_regulation_of_Bcl_2","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/17042173/Withaferin_A_induces_apoptosis_in_human_melanoma_cells_through_generation_of_reactive_oxygen_species_and_down_regulation_of_Bcl_2"><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="7278222" 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/7278222/Withanolide_induces_apoptosis_in_HL60_leukemia_cells_via_mitochondria_mediated_cytochrome_c_release_and_caspase_activation">Withanolide induces apoptosis in HL60 leukemia cells via mitochondria mediated cytochrome c release and caspase activation</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="12709603" href="https://uohyd.academia.edu/BRamadevi">B Ramadevi</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Chemico-biological Interactions, 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":"Withanolide induces apoptosis in HL60 leukemia cells via mitochondria mediated cytochrome c release and caspase activation","attachmentId":48540310,"attachmentType":"pdf","work_url":"https://www.academia.edu/7278222/Withanolide_induces_apoptosis_in_HL60_leukemia_cells_via_mitochondria_mediated_cytochrome_c_release_and_caspase_activation","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/7278222/Withanolide_induces_apoptosis_in_HL60_leukemia_cells_via_mitochondria_mediated_cytochrome_c_release_and_caspase_activation"><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="92717815" 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/92717815/Withaferin_A_inhibits_apoptosis_via_activated_Akt_mediated_inhibition_of_oxidative_stress">Withaferin A inhibits apoptosis via activated Akt-mediated inhibition of oxidative stress</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="198574942" href="https://independent.academia.edu/CaoXiaoming">Xiaoming Cao</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Life sciences, 2018</p><p class="ds-related-work--abstract ds2-5-body-sm">Withaferin A (WFA), a withanolide derived from medicinal plant Withania somnifera, possesses anti-tumorigenic and immunomodulatory activities against various cancer cells. However, the role of WFA in myocardial ischemia reperfusion (MI/R) injury remains unclear. In the present study, we determined whether WFA may regulate cardiac ischemia reperfusion injury and elucidate the underlying mechanisms. We demonstrated that WFA enhanced H9c2 cells survival ability against simulated ischemia/reperfusion (SI/R) or hydrogen peroxide (HO)-induced cell apoptosis. In addition, the enhanced oxidative stress induced by SI/R was inhibited by WFA. Among the multiple antioxidant molecules determined, antioxidants SOD2, SOD3, Prdx-1 was obviously upregulated by WFA. When Akt inhibitor IV was administrated, WFA&#39;s suppression effect on oxidative stress was obviously abolished. Additional experiments demonstrated that WFA successfully inhibited HO induced upregulation of SOD2, SOD3, and Prdx-1, amel...</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":"Withaferin A inhibits apoptosis via activated Akt-mediated inhibition of oxidative stress","attachmentId":95652599,"attachmentType":"pdf","work_url":"https://www.academia.edu/92717815/Withaferin_A_inhibits_apoptosis_via_activated_Akt_mediated_inhibition_of_oxidative_stress","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/92717815/Withaferin_A_inhibits_apoptosis_via_activated_Akt_mediated_inhibition_of_oxidative_stress"><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="8581336" 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/8581336/Withaferin_A_induces_apoptosis_by_activating_p38_mitogen_activated_protein_kinase_signaling_cascade_in_leukemic_cells_of_lymphoid_and_myeloid_origin_through_mitochondrial_death_cascade">Withaferin A induces apoptosis by activating p38 mitogen-activated protein kinase signaling cascade in leukemic cells of lymphoid and myeloid origin through mitochondrial death cascade</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="17716777" href="https://independent.academia.edu/AvijitDutta3">Avijit Dutta</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Apoptosis, 2008</p><p class="ds-related-work--abstract ds2-5-body-sm">Withaferin A (WA) is present abundantly in Withania somnifera, a well-known Indian medicinal plant. Here we demonstrate how WA exhibits a strong growth-inhibitory effect on several human leukemic cell lines and on primary cells from patients with lymphoblastic and myeloid leukemia in a dose-dependent manner, showing no toxicity on normal human lymphocytes and primitive hematopoietic progenitor cells. WA-mediated decrease in cell viability was observed through apoptosis as demonstrated by externalization of phosphatidylserine, a time-dependent increase in Bax/Bcl-2 ratio; loss of mitochondrial transmembrane potential, cytochrome c release, caspases 9 and 3 activation; and accumulation of cells in sub-G0 region based on DNA fragmentation. A search for the downstream pathway further reveals that WA-induced apoptosis was mediated by an increase in phosphorylated p38MAPK expression, which further activated downstream signaling by phosphorylating ATF-2 and HSP27 in leukemic cells. The RNA interference of p38MAPK protected these cells from WA-induced apoptosis. The RNAi knockdown of p38MAPK inhibited active phosphorylation of p38MAPK, Bax expression, activation of caspase 3 and increase in Annexin V positivity. Altogether, these findings suggest that p38MAPK in leukemic cells promotes WA-induced apoptosis. WA caused increased levels of Bax in response to MAPK signaling, which resulted in the initiation of mitochondrial death cascade, and therefore it holds promise as a new, alternative, inexpensive chemotherapeutic agent for the treatment of patients with leukemia of both lymphoid and myeloid origin.</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":"Withaferin A induces apoptosis by activating p38 mitogen-activated protein kinase signaling cascade in leukemic cells of lymphoid and myeloid origin through mitochondrial death cascade","attachmentId":48050827,"attachmentType":"pdf","work_url":"https://www.academia.edu/8581336/Withaferin_A_induces_apoptosis_by_activating_p38_mitogen_activated_protein_kinase_signaling_cascade_in_leukemic_cells_of_lymphoid_and_myeloid_origin_through_mitochondrial_death_cascade","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/8581336/Withaferin_A_induces_apoptosis_by_activating_p38_mitogen_activated_protein_kinase_signaling_cascade_in_leukemic_cells_of_lymphoid_and_myeloid_origin_through_mitochondrial_death_cascade"><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="84934460" 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/84934460/Withaferin_A_mediated_apoptosis_in_breast_cancer_cells_is_associated_with_alterations_in_mitochondrial_dynamics">Withaferin A-mediated apoptosis in breast cancer cells is associated with alterations in mitochondrial dynamics</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="49713377" href="https://independent.academia.edu/SumanSamanta2">Suman Samanta</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Mitochondrion, 2019</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":"Withaferin A-mediated apoptosis in breast cancer cells is associated with alterations in mitochondrial dynamics","attachmentId":89791134,"attachmentType":"pdf","work_url":"https://www.academia.edu/84934460/Withaferin_A_mediated_apoptosis_in_breast_cancer_cells_is_associated_with_alterations_in_mitochondrial_dynamics","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/84934460/Withaferin_A_mediated_apoptosis_in_breast_cancer_cells_is_associated_with_alterations_in_mitochondrial_dynamics"><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="53230474" 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/53230474/The_effects_of_Withania_somnifera_on_the_mitochondria_of_breast_cancer_cell_line_MDA_MB231">The effects of Withania somnifera on the mitochondria of breast cancer cell line MDA MB231</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="185041693" href="https://independent.academia.edu/NikitaAgarwal130">Nikita Agarwal</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Master's Thesis, 2019</p><p class="ds-related-work--abstract ds2-5-body-sm">Breast cancer is the second most common cancer affecting over 2 million people each year. About 20% of these cases are negative for HER2, PR and ER expression i.e. triple-negative breast cancer TNBC. These cells lack receptors for the drug to act on and hence require a different metabolic pathway target. The mitochondria have a significant role to play in cancer proliferation. Its dysfunction is said to cause apoptosis in cancer cells. Withaferin A, a compound found in Withania somnifera root is shown to have anti-cancer properties. Aim - The purpose of this dissertation is to study the effects of Withania somnifera methanolic extract on human breast cancer cells. To test whether treatment with the extract for 1 h causes mitochondrial dysfunction in MDA MB231 cells. Methods –MDA MB231 breast cancer cells were treated with 10 μg/mL of the extract for 1 hour. Changes in mitochondrial respiration were investigated using the MitoStress assay employing the SeaHorse XFe24 Analyser. Coupled with the Bradford assay for protein estimation to correct variations in the cell population. The reactive oxygen species ROS production and mitochondrial membrane potential MMP was measured using fluorescent spectroscopy. Results – There were no significant changes observed in the treated cells when compared to the control. Basal respiration, spare respiratory capacity, proton leak, maximum respiration and ATP production was seen to increase by approximately 50% (p > 0.05) i.e. not significant. Non-mitochondrial respiration showed a 21.15% (p = 0.489) rise. ROS production and MMP was not altered by the treatment when compared to DMSO. Conclusion – The experimental data suggest that 10 μg/mL of W. somnifera methanolic extract does not cause mitochondrial dysfunction in MDA MB231 cells after 1-hour treatment. Further studies of the effect of W. somnifera on different metabolic pathways of the mitochondrial are required for confirmation.</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":"The effects of Withania somnifera on the mitochondria of breast cancer cell line MDA MB231","attachmentId":70118555,"attachmentType":"pdf","work_url":"https://www.academia.edu/53230474/The_effects_of_Withania_somnifera_on_the_mitochondria_of_breast_cancer_cell_line_MDA_MB231","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/53230474/The_effects_of_Withania_somnifera_on_the_mitochondria_of_breast_cancer_cell_line_MDA_MB231"><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="14864970" 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/14864970/Immune_modulation_and_apoptosis_induction_Two_sides_of_antitumoural_activity_of_a_standardised_herbal_formulation_of_Withania_somnifera">Immune modulation and apoptosis induction: Two sides of antitumoural activity of a standardised herbal formulation of Withania somnifera</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="33838613" href="https://independent.academia.edu/ShashiBhushan44">Shashi Bhushan</a></div><p class="ds-related-work--metadata ds2-5-body-xs">European Journal of Cancer, 2009</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":"Immune modulation and apoptosis induction: Two sides of antitumoural activity of a standardised herbal formulation of Withania somnifera","attachmentId":43830903,"attachmentType":"pdf","work_url":"https://www.academia.edu/14864970/Immune_modulation_and_apoptosis_induction_Two_sides_of_antitumoural_activity_of_a_standardised_herbal_formulation_of_Withania_somnifera","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/14864970/Immune_modulation_and_apoptosis_induction_Two_sides_of_antitumoural_activity_of_a_standardised_herbal_formulation_of_Withania_somnifera"><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="28997322" 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/28997322/Withaferin_A_A_Potential_Anticancer_Withanolide_from_Withania_somnifera_L_Dun">Withaferin-A: A Potential Anticancer Withanolide from Withania somnifera (L.) Dun</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="54506350" href="https://independent.academia.edu/AmritSingh87">Amrit Singh</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Ethnobotanical Leaflets, 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":"Withaferin-A: A Potential Anticancer Withanolide from Withania somnifera (L.) Dun","attachmentId":49444222,"attachmentType":"pdf","work_url":"https://www.academia.edu/28997322/Withaferin_A_A_Potential_Anticancer_Withanolide_from_Withania_somnifera_L_Dun","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/28997322/Withaferin_A_A_Potential_Anticancer_Withanolide_from_Withania_somnifera_L_Dun"><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="52375872" 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/52375872/Antioxidant_activity_and_apoptotic_induction_as_mechanisms_of_action_of_Withania_somnifera_Ashwagandha_against_a_hepatocellular_carcinoma_cell_line">Antioxidant activity and apoptotic induction as mechanisms of action of Withania somnifera (Ashwagandha) against a hepatocellular carcinoma cell line</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="477707" href="https://cairo.academia.edu/SalwaSabet">Salwa Sabet</a></div><p class="ds-related-work--metadata ds2-5-body-xs">The Journal of international medical research, 2018</p><p class="ds-related-work--abstract ds2-5-body-sm">Objective To evaluate the antioxidant and apoptotic inductive effects of Withania somnifera (Ashwagandha) leaf extract against a hepatocellular carcinoma cell line. Methods After treating HepG2cells with Ashwagandha water extract (ASH-WX; 6.25 mg/ml-100 mg/ml), cell proliferation was assessed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Antioxidant activities (total antioxidant, glutathione S-transferase and glutathione reductase), Fas-ligand level, tumour necrosis factor-α (TNF-α) level and caspase-3, -8, and -9 activities were measured. Molecular modelling assessed the binding-free energies of Ashwagandha in the cyclin D1 receptor. Results The MTT assay demonstrated increased cytotoxicity following treatment of HepG2 cells with ASH-WX compared with control untreated cells and theICwas 5% (approximately 5.0 mg/ml). Antioxidant activities, Fas-ligand levels and caspase-3, -8 and -9 activities significantly increased, while TNF-α level significant...</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":"Antioxidant activity and apoptotic induction as mechanisms of action of Withania somnifera (Ashwagandha) against a hepatocellular carcinoma cell line","attachmentId":69668614,"attachmentType":"pdf","work_url":"https://www.academia.edu/52375872/Antioxidant_activity_and_apoptotic_induction_as_mechanisms_of_action_of_Withania_somnifera_Ashwagandha_against_a_hepatocellular_carcinoma_cell_line","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/52375872/Antioxidant_activity_and_apoptotic_induction_as_mechanisms_of_action_of_Withania_somnifera_Ashwagandha_against_a_hepatocellular_carcinoma_cell_line"><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":46476855,"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":46476855,"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_46476855" 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="114963621" 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/114963621/A_critical_review_of_anticancer_properties_of_Withania_somnifera_L_Dunal_with_respect_to_the_biochemical_mechanisms_of_its_phytochemical_constituents">A critical review of anticancer properties of Withania somnifera (L.) 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