title: Pachymic acid inhibits the tumorigenicity of gastric cancer cells by the mitochondrial pathway.
abstract: Pachymic acid (PA), a lanostane-type triterpenoid derived from traditional Chinese herbals, has been reported to have antitumor activity in versatile cancer cells. However, the antitumor effect of PA in gastric cancer (GC) cells remains unclear. In this study, we aimed to explore the efficacy and mechanisms of PA in GC. The antiproliferative effect of PA was assessed by a growth assay and a colony formation assay. Flow cytometry was used to detect changes in cell cycle distribution. Apoptosis was assessed by an annexin V/propidium iodide double-staining assay. The expressions of the apoptosis-related proteins were measured by western blot. The mitochondrial capacity was observed by immunostaining of Mito Tracker Red and mitochondrial function protein MT. Xenograft models of GC were constructed by a subcutaneous injection of SGC-7901 and MKN-49P cells pretreated with PA. PA could potently inhibit GC cell growth and colony formation. PA significantly induced G1, G2/M, and inhibited G0 phase arrest in GC cell lines SGC-7901 and MKN-49P. PA induced cell apoptosis by regulating the expressions of apoptosis-related proteins (caspase-3, PARP, Bcl-2, and Bax) and suppressing the mitochondrial capacity of GC cell lines in vitro in a dose-dependent manner. In addition, PA suppressed the tumor growth of xenograft models of GC and prolonged the survival of animals markedly. In brief, the present study shows that PA induces apoptosis through inhibition of mitochondrial capacity in human GC cells. Our findings suggest that PA may have therapeutic potential in GC.
authors: Zhongshan Hospital, Fudan University, Shanghai, China.
authors: Chunwei
authors: C
authors: Lu
authors: Jun
authors: J
authors: Ma
authors: Dingfang
authors: D
authors: Cai
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D014315:Triterpenes / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D014315:Triterpenes; C102487:pachymic acid