Search results for: camptothecin

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style="font-size:.9rem"><span class="badge badge-info">5</span> Camptothecin Promotes ROS-Mediated G2/M Phase Cell Cycle Arrest, Resulting from Autophagy-Mediated Cytoprotection</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Rajapaksha%20Gedara%20Prasad%20Tharanga%20Jayasooriya">Rajapaksha Gedara Prasad Tharanga Jayasooriya</a>, <a href="https://publications.waset.org/abstracts/search?q=Matharage%20Gayani%20Dilshara"> Matharage Gayani Dilshara</a>, <a href="https://publications.waset.org/abstracts/search?q=Yung%20Hyun%20Choi"> Yung Hyun Choi</a>, <a href="https://publications.waset.org/abstracts/search?q=Gi-Young%20Kim"> Gi-Young Kim</a> </p> <p class="card-text"><strong>Abstract:</strong></p> Camptothecin (CPT) is a quinolone alkaloid which inhibits DNA topoisomerase I that induces cytotoxicity in a variety of cancer cell lines. We previously showed that CPT effectively inhibited invasion of prostate cancer cells and also combined treatment with subtoxic doses of CPT and TNF-related apoptosis-inducing ligand (TRAIL) potentially enhanced apoptosis in a caspase-dependent manner in hepatoma cancer cells. Here, we found that treatment with CPT caused an irreversible cell cycle arrest in the G2/M phase. CPT-induced cell cycle arrest was associated with a decrease in protein levels of cell division cycle 25C (Cdc25C) and increased the level of cyclin B and p21. The CPT-induced decrease in Cdc25C was blocked in the presence of proteasome inhibitor MG132, thus reversed the cell cycle arrest. In addition to that treatment of CPT-increased phosphorylation of Cdc25C was the resulted of activation of checkpoint kinase 2 (Chk2), which was associated with phosphorylation of ataxia telangiectasia-mutated. Interestingly CPT induced G2/M phase of the cell cycle arrest is reactive oxygen species (ROS) dependent where ROS inhibitors NAC and GSH reversed the CPT-induced cell cycle arrest. These results further confirm by using transient knockdown of nuclear factor-erythroid 2-related factor 2 (Nrf2) since it regulates the production of ROS. Our data reveal that treatment of siNrf2 increased the ROS level as well as further increased the CPT induce G2/M phase cell cycle arrest. Our data also indicate CPT-enhanced cell cycle arrest through the extracellular signal-regulated kinase (ERK) and the c-Jun N-terminal kinase (JNK) pathway. Inhibitors of ERK and JNK more decreased the Cdc25C expression and protein expression of p21 and cyclin B. These findings indicate that Chk2-mediated phosphorylation of Cdc25C plays a major role in G2/M arrest by CPT. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=camptothecin" title="camptothecin">camptothecin</a>, <a href="https://publications.waset.org/abstracts/search?q=cell%20cycle" title=" cell cycle"> cell cycle</a>, <a href="https://publications.waset.org/abstracts/search?q=checkpoint%20kinase%202" title=" checkpoint kinase 2"> checkpoint kinase 2</a>, <a href="https://publications.waset.org/abstracts/search?q=nuclear%20factor-erythroid%202-related%20factor%202" title=" nuclear factor-erythroid 2-related factor 2"> nuclear factor-erythroid 2-related factor 2</a>, <a href="https://publications.waset.org/abstracts/search?q=reactive%20oxygen%20species" title=" reactive oxygen species"> reactive oxygen species</a> </p> <a href="https://publications.waset.org/abstracts/48508/camptothecin-promotes-ros-mediated-g2m-phase-cell-cycle-arrest-resulting-from-autophagy-mediated-cytoprotection" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/48508.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">441</span> </span> </div> </div> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">4</span> Melanoma Antigen Proteins Are Involved in DNA Damage Response</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Olivier%20de%20Backer">Olivier de Backer</a>, <a href="https://publications.waset.org/abstracts/search?q=Alexis%20Khelfi"> Alexis Khelfi</a>, <a href="https://publications.waset.org/abstracts/search?q=Olivier%20Svensek"> Olivier Svensek</a>, <a href="https://publications.waset.org/abstracts/search?q=Axelle%20Nolmans"> Axelle Nolmans</a>, <a href="https://publications.waset.org/abstracts/search?q=Dominique%20Desnoeck"> Dominique Desnoeck</a> </p> <p class="card-text"><strong>Abstract:</strong></p> The SMC5-SMC6 complex helps replication and repair of DNA double-strand breaks. Nse1, Nse3 and Nse4 are non-SMC components of the complex in which Nse3 stimulates the E3 ubiquitin ligase activity of Nse1 and is required for recruiting the complex on DNA. In most eukaryotes, Nse3 is a single protein, but in eutherians (placental mammals), it belongs to a large family of proteins called MAGE (Melanoma antigen) that share a conserved domain of about 200 aa known as MHD (Mage homology domain). MAGE assembles specific RING and HECT ubiquitin ligases and determines new substrates for ubiquitination. The MHD is required for the interaction with the cognate E3 ligase. Some MAGEs (referred to as Type I) are exclusively expressed in germ cells of the testis but are often expressed ectopically in cancer cells as the result of epigenetic modifications. The 12 MAGE-A genes belong to this category. Serval MAGE-A proteins could promote tumorigenesis by targeting tumor suppressor proteins (including p53) for ubiquitination and degradation. We showed that depletion of MAGE-A proteins in melanoma cells results in impaired DNA damage response and increased double-strand breaks after exposure to camptothecin. Moreover, it was shown that other actors of the DNA Damage Response were impacted when cells were depleted of MAGEA proteins. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=DNA%20damage%20response" title="DNA damage response">DNA damage response</a>, <a href="https://publications.waset.org/abstracts/search?q=melanoma" title=" melanoma"> melanoma</a>, <a href="https://publications.waset.org/abstracts/search?q=camptothecin" title=" camptothecin"> camptothecin</a>, <a href="https://publications.waset.org/abstracts/search?q=new%20role" title=" new role"> new role</a>, <a href="https://publications.waset.org/abstracts/search?q=MAGEA" title=" MAGEA"> MAGEA</a> </p> <a href="https://publications.waset.org/abstracts/169692/melanoma-antigen-proteins-are-involved-in-dna-damage-response" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/169692.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">101</span> </span> </div> </div> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">3</span> Effects of New Anthraquinone Derivatives on Resistance Ovarian Cancer Cells and The Mechanism Investigation</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Hui-Hsin%20Huang">Hui-Hsin Huang</a>, <a href="https://publications.waset.org/abstracts/search?q=Sheng-Tung%20Huang"> Sheng-Tung Huang</a>, <a href="https://publications.waset.org/abstracts/search?q=Chi-Ming%20Lee"> Chi-Ming Lee</a>, <a href="https://publications.waset.org/abstracts/search?q=Chiao-Han%20Yen"> Chiao-Han Yen</a>, <a href="https://publications.waset.org/abstracts/search?q=Chun-Mao%20Lin"> Chun-Mao Lin</a> </p> <p class="card-text"><strong>Abstract:</strong></p> At initiation stage, there are no symptoms at initiation stage; however, at late stage, patients suffer symptoms as soon as ovarian cancer metastasis. Moreover, ovarian cancer cells are resistant to some anti-ovarian cancer drugs in clinical. Thus, it is very important to find an effective treatment for resistant ovarian cancer. Anthraquinone derivatives are able to induce DNA damage and lead to cell apoptosis, so several derivatives have been used for clinical application. Therefore, to explore more effective anti-ovarian cancer drugs, this study investigates the mechanism of three new anthraquinone compounds bearing different functional groups to camptothecin-resistance ovarian cell line A2780R2000. Cell viability was determined by MTT assay after treating A2780R2000 with the three new anthraquinone compounds. The results indicated that IC50 values are 33.44μM (Compound I), 25.77μM (Compound II) and 24.59μM (Compound III). Next, through cell cycle analysis, the results demonstrated that three new anthraquinone compounds not only induced A2780R2000 cell cycle arrest at early stage but also apoptosis at late stage. Besides, through apoptosis assay, the results indicated new anthraquinone compound induced apoptosis at late stage. Furthermore, the results of western blot show that the three new anthraquinone compounds lead to A2780R2000 apoptosis through intrinsic pathway. Theses results suggested that three new anthraquinone compounds may be potential new drugs for clinical cancer treatment in the future. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=anthraquinone" title="anthraquinone">anthraquinone</a>, <a href="https://publications.waset.org/abstracts/search?q=camptothecin" title=" camptothecin"> camptothecin</a>, <a href="https://publications.waset.org/abstracts/search?q=resistance" title=" resistance"> resistance</a>, <a href="https://publications.waset.org/abstracts/search?q=ovarian%20cancer" title=" ovarian cancer"> ovarian cancer</a> </p> <a href="https://publications.waset.org/abstracts/44883/effects-of-new-anthraquinone-derivatives-on-resistance-ovarian-cancer-cells-and-the-mechanism-investigation" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/44883.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">394</span> </span> </div> </div> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">2</span> Role of Natural Products in Drug Discovery of Anti-Biotic and Anti-Cancer Agents</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Sunil%20Kumar">Sunil Kumar</a> </p> <p class="card-text"><strong>Abstract:</strong></p> For many years, small organic molecules derived naturally from microbes and plants have delivered a number of expedient therapeutic drug agents. The search for naturally occurring lead compounds has continued in recent years as well, with the constituents of marine flora and fauna along with those of telluric microorganisms and plants being investigated for their anti-bacterial and anti-cancer activities. It has been observed that such promising lead molecules incline to promptly generate substantial attention among scientists like synthetic organic chemists and biologists. Subsequently, the availability of a given precious natural product sample may be enriched, and it may be possible to determine a preliminary idea of structure-activity relationships to develop synthetic analogues. For instance, anti-tumor drug topotecan is a synthetic chemical compound similar in chemical structure to camptothecin which is found in extracts of Camptotheca acuminate. Similarly, researchers at AstraZeneca discovered anti-biotic pyrrolamide through a fragment-based lead generation approach from kibdelomycin, which is isolated from Staphylococcus aureuss. <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=anticancer" title="anticancer">anticancer</a>, <a href="https://publications.waset.org/abstracts/search?q=antibiotic" title=" antibiotic"> antibiotic</a>, <a href="https://publications.waset.org/abstracts/search?q=lead%20molecule" title=" lead molecule"> lead molecule</a>, <a href="https://publications.waset.org/abstracts/search?q=natural%20product" title=" natural product"> natural product</a>, <a href="https://publications.waset.org/abstracts/search?q=synthetic%20analogues" title=" synthetic analogues"> synthetic analogues</a> </p> <a href="https://publications.waset.org/abstracts/97413/role-of-natural-products-in-drug-discovery-of-anti-biotic-and-anti-cancer-agents" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/97413.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">152</span> </span> </div> </div> <div class="card paper-listing mb-3 mt-3"> <h5 class="card-header" style="font-size:.9rem"><span class="badge badge-info">1</span> New 5’-O- and 6-Substituted Purine Nucleoside Analogs: Synthesis and Cytotoxic Activity on Selected Human Cancer Cell Lines</h5> <div class="card-body"> <p class="card-text"><strong>Authors:</strong> <a href="https://publications.waset.org/abstracts/search?q=Meral%20Tuncbilek">Meral Tuncbilek</a>, <a href="https://publications.waset.org/abstracts/search?q=Duygu%20Sac"> Duygu Sac</a>, <a href="https://publications.waset.org/abstracts/search?q=Irem%20Durmaz"> Irem Durmaz</a>, <a href="https://publications.waset.org/abstracts/search?q=Rengul%20Cetin%20Atalay"> Rengul Cetin Atalay</a> </p> <p class="card-text"><strong>Abstract:</strong></p> Nucleoside analogs are a pharmacologically diverse family that includes cytotoxic compounds, antiviral agents, and immunosuppressive molecules. Purine nucleoside derivatives such as fludarabine, cladribine, and pentostatin are significant drugs used in chemotherapy for the treatment of solid tumors and hematological malignancies. In this study, we synthesized novel purine ribonucleoside analogs containing a 4-(4-substituted phenylsulfonyl) piperazine in the substituent at N6- and O-substituted sulfonyl group at 5’-position as putative cytotoxic agents. The newly obtained compounds were then characterized for their cytotoxicity in human cancer cell lines. The 5’, 6-disubstituted 9-(β-D-ribofuranosyl)purine derivatives (44-67) were readily obtained from commercially available inosine in seven steps in very cost effective synthesis approach. The newly synthesized compounds were first evaluated for their anti-tumor activities against human liver (Huh7), colon (HCT116) and breast (MCF7) carcinoma cell lines. The IC50 values were in micromolar concentrations with 5’, 6-disubstituted purine nucleoside derivatives. Time-dependent IC50 values for each molecule were also calculated in comparison with known cytotoxic agents Camptothecin (CPT), 5-Fluorouracil (5-FU), Cladribine, Pentostatine and Fludarabine. N6-(4-trifluoromethyl phenyl) / N6-(4-bromophenyl) and 5’-O-(4-methoxybenzene sulfonyl) / 5’-O-(benzenesulfonyl) derivatives 54, 64 displayed the best cytotoxic activity with IC50 values of 8.8, 7 µM against MCF7 cell line. The N6-(4-methylphenyl) analog 50 was also very active (IC50= 10.7 μM) against HCT116 cell line. Furthermore, compound 64 had a better cytotoxic activity than the known cell growth inhibitors 5-FU and Fludarabine on Huh7 (1.5 vs 30.7, 29.9 μM for 5-FU and Fludarabine). <p class="card-text"><strong>Keywords:</strong> <a href="https://publications.waset.org/abstracts/search?q=cytotoxic%20activity" title="cytotoxic activity">cytotoxic activity</a>, <a href="https://publications.waset.org/abstracts/search?q=Huh7" title=" Huh7"> Huh7</a>, <a href="https://publications.waset.org/abstracts/search?q=HCT116" title=" HCT116"> HCT116</a>, <a href="https://publications.waset.org/abstracts/search?q=MCF7" title=" MCF7"> MCF7</a>, <a href="https://publications.waset.org/abstracts/search?q=nucleoside" title=" nucleoside"> nucleoside</a>, <a href="https://publications.waset.org/abstracts/search?q=synthesis" title=" synthesis"> synthesis</a> </p> <a href="https://publications.waset.org/abstracts/49693/new-5-o-and-6-substituted-purine-nucleoside-analogs-synthesis-and-cytotoxic-activity-on-selected-human-cancer-cell-lines" class="btn btn-primary btn-sm">Procedia</a> <a href="https://publications.waset.org/abstracts/49693.pdf" target="_blank" class="btn btn-primary btn-sm">PDF</a> <span class="bg-info text-light px-1 py-1 float-right rounded"> Downloads <span class="badge badge-light">242</span> </span> </div> </div> </div> </main> <footer> <div id="infolinks" class="pt-3 pb-2"> <div class="container"> <div style="background-color:#f5f5f5;" class="p-3"> <div class="row"> <div class="col-md-2"> <ul class="list-unstyled"> About <li><a href="https://waset.org/page/support">About Us</a></li> <li><a href="https://waset.org/page/support#legal-information">Legal</a></li> <li><a target="_blank" rel="nofollow" href="https://publications.waset.org/static/files/WASET-16th-foundational-anniversary.pdf">WASET celebrates its 16th foundational 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Search results for: camptothecin