Marsdeniae tenacissima extract-induced growth inhibition and apoptosis in hepatoma carcinoma cells is mediated through the p53/nuclear factor-κB signaling pathway

Abstract

An extract from a traditional Chinese herb, Marsdeniae tenacissima (trade name, Xiao-Ai-Ping) has been approved for use on the Chinese market as a cancer chemotherapeutic agent for decades. Previous studies have demonstrated the cytostatic and pro-apoptotic effects of M. tenacissima extract (MTE) in multiple cancer cells. However, the contributions of MTE to the proliferation and apoptosis of hepatoma carcinoma cells and the underlying mechanisms remain unclear. In the present study, Bel-7402 cells were incubated with increasing concentrations of MTE ranging from 0–320 µl/ml to explore the effects and potential mechanisms of MTE on the proliferation and apoptosis of Bel-7402 cells. 3-(4,5-dimethylthiazol-2-yl)-5(3-carboxymethoxyphenyl)-2-(4-sulfopheny)-2H-tetrazolium, inner salt and propidium iodide (PI)-stained flow cytometry assays demonstrated that MTE significantly suppressed the proliferation of Bel-7402 cells in a dose-dependent manner by arresting the cell cycle at S phase (P<0.05). Annexin V-fluorescein isothiocyanate PI-stained flow cytometry confirmed the significantly pro-apoptotic effect of MTE at both 160 and 240 µl/ml (P<0.001). Reverse transcription-quantitative polymerase chain reaction and western blot analysis demonstrated that MTE (both 160 and 240 µl/ml) induced a significant downregulation of B-cell lymphoma (Bcl)-2 (P<0.01), upregulation of Bcl-2-associated X protein (P<0.01) and activation of caspase-3 (P<0.05). Furthermore, a significant downregulation of murine double minute-2 (MDM2) (P<0.001) and activation of p53 (P<0.001) in Bel-7402 cells following treatment with 160 or 240 µl/ml MTE was observed, accompanied by the inhibition of the nuclear factor (NF)-κB pathway (P<0.001). These results suggested that MTE inhibited growth and exhibited pro-apoptotic effects in Bel-7402 cells, which was mediated by downregulation of the MDM2-induced p53-dependent mitochondrial apoptosis pathway and blocking the NF-κB pathway. Overall, these data serve as preliminary identification of the significant roles of MTE in hepatic carcinoma cells, and suggest that MTE may be a promising candidate for hepatocellular carcinoma therapy.

C21 Fraction Refined from Marsdenia tenacissima-Induced Apoptosis is Enhanced by Suppression of Autophagy in Human Gastric Cell Lines

“…Marsdenia tenacissima is an asclepiadaceous plant that is widely produced in China. Its liquid extracts (trade name: Xiao Ai Ping) have been approved to treat esophageal cancer, lung cancer, leukemia, hepatocellular carcinoma, and gastric cancer. , We found that C21 steroidal glycosides are widely found in MTE, and this study’s authors’ previous work has shown that treatment with C21 fraction from M. tenacissima could induce cell apoptosis through the PTEN-AKT-mTOR signal pathway .…”

“…Its liquid extracts (trade name: Xiao Ai Ping) have been approved to treat esophageal cancer, lung cancer, leukemia, hepatocellular carcinoma, and gastric cancer. 13,14 We found that C21 steroidal glycosides are widely found in MTE, and this study's authors' previous work has shown that treatment with C21 fraction from M. tenacissima could induce cell apoptosis through the PTEN-AKT-mTOR signal pathway. 15 promote the anticancer effects of C21 has not yet been investigated.…”