title: Chaetoglobosin K induces apoptosis and G2 cell cycle arrest through p53-dependent pathway in cisplatin-resistant ovarian cancer cells.
abstract: Adverse side effects and acquired resistance to conventional platinum based chemotherapy have become major impediments in ovarian cancer treatment, and drive the development of more selective anticancer drugs. Chaetoglobosin K (ChK) was shown to have a more potent growth inhibitory effect than cisplatin on two cisplatin-resistant ovarian cancer cell lines, OVCAR-3 and A2780/CP70, and was less cytotoxic to a normal ovarian cell line, IOSE-364, than to the cancer cell lines. Hoechst 33342 staining and Flow cytometry analysis indicated that ChK induced preferential apoptosis and G2 cell cycle arrest in both ovarian cancer cells with respect to the normal ovarian cells. ChK induced apoptosis through a p53-dependent caspase-8 activation extrinsic pathway, and caused G2 cell cycle arrest via cyclin B1 by increasing p53 expression and p38 phosphorylation in OVCAR-3 and A2780/CP70 cells. DR5 and p21 might play an important role in determining the sensitivity of normal and malignant ovarian cells to ChK. Based on these results, ChK would be a potential compound for treating platinum-resistant ovarian cancer.
authors.affiliation: College of Science, Technology and Mathematics, Alderson Broaddus University, Philippi, WV 26416, USA; Department of Tea Science, Zhejiang University, Hangzhou 310058, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.affiliation: College of Science, Technology and Mathematics, Alderson Broaddus University, Philippi, WV 26416, USA; Department of Tea Science, Zhejiang University, Hangzhou 310058, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Pharmacology, Physiology and Toxicology, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25755, USA.
authors.forename: Gary O
authors.initials: GO
authors.lastname: Rankin
authors.affiliation: Department of Pharmaceutical Science, West Virginia University, Morgantown, WV 26506, USA.
authors.forename: Yon
authors.initials: Y
authors.lastname: Rojanasakul
authors.affiliation: Department of Medicinal Chemistry, University of Mississippi, University, MS 38677, USA.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Cutler
authors.affiliation: Department of Tea Science, Zhejiang University, Hangzhou 310058, China. Electronic address: youytu@zju.edu.cn.
authors.forename: Youying
authors.initials: Y
authors.lastname: Tu
authors.affiliation: College of Science, Technology and Mathematics, Alderson Broaddus University, Philippi, WV 26416, USA. Electronic address: chenyc@ab.edu.
authors.forename: Yi Charlie
authors.initials: YC
authors.lastname: Chen
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D005434:Flow Cytometry; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D006801:Humans; D007124:Immunoenzyme Techniques; D026121:Indole Alkaloids / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D026121:Indole Alkaloids; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C019290:chaetoglobosins; D002945:Cisplatin
keywords: Apoptosis; Cell cycle arrest; Chaetoglobosin K; Ovarian cancer; p38; p53