title: Cytotoxicity of tubeimoside I in human choriocarcinoma JEG-3 cells by induction of cytochrome c release and apoptosis via the mitochondrial-related signaling pathway.
abstract: Mitochondria play important roles in the intrinsic pathways that trigger apoptosis. Anticancer chemotherapies eliminate cancer cells mainly through the induction of apoptosis. In the present study, we investigated the mechanism of the cytotoxic effects of tubeimoside I (TBMS1) on the human choriocarcinoma cell line (JEG-3). Choriocarcinoma is one of the most common malignant tumors in the reproductive system. TBMS1, a triterpenoid saponin, isolated from the tubers of Bolbostemma paniculatum (Maxim) Franquet (Cucurbitaceae), showed potent antitumor effects. However, the potential roles of TBMS1 in the treatment of choriocarcinoma remain unknown. In the present study, we examined the effects of TBMS1 on JEG-3 cells. TBMS1 displayed strong growth inhibitory effects on JEG-3 cell growth. In addition, TBMS1 treatment with TBMS1 led to marked cell apoptosis, significant cell cycle arrest at G2 phase and decrease in mitochondrial transmembrane potential (ΔΨm). Cytochrome c was released from the mitochondria and caspase-3 expression was enhanced. Furthermore, TBMS1 induced the up-regulation of Bcl-2 associated X protein (Bax) expression, down-regulation of Bcl-2 expression, inhibition of nuclear factor-κ-B (NF-κB) function and impacted the phosphorylation of p38 mitogen-activated protein kinase (p38/MAPK), extracellular signal-regulated kinases (ERK)1/2 and protein kinase B (Akt). Taken together, our findings suggest that TBMS1 is an efficient apoptosis-inducing agent for choriocarcinoma cells, which exerts its effects, at least partially, by the induction of mitochondrial dysfunction and regulation of the p38/MAPK, ERK1/2 and PI3K/Akt signaling pathways.
authors.affiliation: Laboratory of Reproductive Biology, School of Public Health, Chongqing Medical University, Chongqing 400016, PR China.
authors.forename: Pei
authors.initials: P
authors.lastname: Huang
authors.forename: Chao
authors.initials: C
authors.lastname: Yu
authors.forename: Xue-Qing
authors.initials: XQ
authors.lastname: Liu
authors.forename: Yu-Bin
authors.initials: YB
authors.lastname: Ding
authors.forename: Ying-Xiong
authors.initials: YX
authors.lastname: Wang
authors.forename: Jun-Lin
authors.initials: JL
authors.lastname: He
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002822:Choriocarcinoma / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D018613:Microscopy, Confocal; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012503:Saponins / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: D012503:Saponins; D014315:Triterpenes; C051084:tubeimoside I; D045304:Cytochromes c; D002118:Calcium