title: Triptolide induces apoptosis of gastric cancer cells via inhibiting the overexpression of MDM2.
abstract: Triptolide has been reported to exhibit antitumor effects in several cancers. This study investigates the mechanism by which triptolide induces apoptosis of gastric cancer cells. Gastric biopsies were collected for histological evaluation and detection of murine double minute 2 (MDM2) expression. Gastric cancer cells were cultured and treated with different concentrations of triptolide at indicated time points. The expression of MDM2, p53 protein, and target proteins including p21, PUMA, and X-linked inhibitor of apoptosis protein (XIAP) was detected. Apoptosis of cells treated with or without triptolide was evaluated. Our results showed that MDM2 protein was overexpressed in gastric cancer (p < 0.01, resp.). Triptolide induced significant apoptosis of gastric cancer cells in a dose- and time-dependent manner (p < 0.05). In addition, treatment with triptolide strongly inhibited the overexpression of MDM2 in gastric cancer cells, and this MDM2 inhibition led to increased levels of p53 protein and inhibition of XIAP (p < 0.05). However, triptolide failed to increase the expression of p53 target protein p21 and PUMA (p > 0.05). In conclusion, triptolide may induce apoptosis of gastric cancer cells via the inhibition of MDM2 overexpression in a p53-independent manner.
authors.affiliation: Department of General Surgery, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan, 430071, Hubei, China.
authors.forename: Bo-Yong
authors.initials: BY
authors.lastname: Wang
authors.forename: Jun
authors.initials: J
authors.lastname: Cao
authors.forename: Ji-Wei
authors.initials: JW
authors.lastname: Chen
authors.forename: Quan-Yan
authors.initials: QY
authors.lastname: Liu
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D014408:Biomarkers, Tumor / Q000096:biosynthesis; D004224:Diterpenes / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004852:Epoxy Compounds / Q000494:pharmacology / Q000627:therapeutic use; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D010616:Phenanthrenes / Q000494:pharmacology* / Q000627:therapeutic use; D051736:Proto-Oncogene Proteins c-mdm2 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D018906:Antineoplastic Agents, Alkylating; D014408:Biomarkers, Tumor; D004224:Diterpenes; D004852:Epoxy Compounds; D010616:Phenanthrenes; C001899:triptolide; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2