title: Triptolide induces apoptosis in endometrial cancer via a p53‑independent mitochondrial pathway.
abstract: Triptolide (TP), the primary active component purified from the traditional Chinese herbal medicine Tripterygium wilfordii Hook. F (TWHF), has been shown to possess antitumor activity in several types of solid tumors. In the present study, we investigated the antitumor effect of TP in human endometrial cancer cells (HEC-1B) and elucidated its possible underlying mechanisms. HEC-1B cells were treated with various doses of TP (10, 20, 40, 80, 160 and 320 nM), and the cell viability was assessed by Cell Counting Kit-8 (CCK-8) and flow cytometric analysis. Results indicated that TP inhibited the proliferation of HEC-1B cells in a dose- and time‑dependent manner. To further investigate its mechanisms, the levels of apoptosis and the changes in caspase-3/9 expression in HEC-1B cells by pretreatment with z-VAD-fmk, a pan-caspase inhibitor, were detected by CCK-8 and western blotting. The cytotoxic effects of TP were significantly inhibited by z-VAD‑fmk. At the molecular level, TP did not effectively activate the p53 signaling pathway, but upregulated caspase-3/9 and downregulated bcl-2 without changing the bax level. Our studies revealed that TP has an effect on the apoptotic ability of endometrial cancer cells via a p53-independent mitochondrial pathway, presenting a novel strategy to evade drug resistance in tumorigenesis. The ability of TP to be a potential chemotherapeutic agent for endometrial cancer should be considered.
authors.affiliation: Changzhou Maternal and Child Health Care Hospital of Nanjing Medical University, Changzhou 213003, P.R. China.
authors.forename: Xiao-Fei
authors.initials: XF
authors.lastname: Wang
authors.forename: Yi-Bing
authors.initials: YB
authors.lastname: Zhao
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wu
authors.forename: Zhi-Hua
authors.initials: ZH
authors.lastname: Sun
authors.forename: Hai-Jin
authors.initials: HJ
authors.lastname: Li
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000737:chemistry / Q000378:metabolism; D053453:Caspase 9 / Q000737:chemistry / Q000378:metabolism; D045744:Cell Line, Tumor; D004224:Diterpenes / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D016889:Endometrial Neoplasms / Q000378:metabolism / Q000473:pathology; D004852:Epoxy Compounds / Q000494:pharmacology; D005260:Female; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D010616:Phenanthrenes / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D018906:Antineoplastic Agents, Alkylating; D004224:Diterpenes; D004852:Epoxy Compounds; D010616:Phenanthrenes; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; C001899:triptolide; D053148:Caspase 3; D053453:Caspase 9