Fangchinoline abrogates growth and survival of hepatocellular carcinoma by negative regulation of c-met/HGF and its associated downstream signaling pathways

Among all cancers, hepatocellular carcinoma (HCC) remains a lethal disease with limited treatment options. In this study, we have analyzed the possible inhibitory effects of Fangchinoline (FCN) on c-Met, a protein known to regulate the rapid phosphorylation of downstream signals, as well as mediate aberrant growth, metastasis, survival, and motility in cancer. FCN inhibited the activation of c-Met and its downstream signals PI3K, AKT, mTOR, MEK, and ERK under in vitro settings. Moreover, c-Met gene silencing lead to suppression of PI3K/AKT/mTOR and MEK/ERK signaling pathways, and induced apoptotic cell death upon exposure to FCN. In addition, FCN markedly inhibited the expression of the various oncogenic proteins such as Bcl-2/xl, survivin, IAP-1/2, cyclin D1, and COX-2. In vivo studies in HepG2 cells xenograft mouse model showed that FCN could significantly attenuate the tumor volume and weight, without affecting significant loss in the body weight. Similar to in vitro studies, expression level of c-Met and PI3K/AKT/mTOR, MEK/ERK signals was also suppressed by FCN in the tissues obtained from mice. Therefore, the novel findings of this study suggest that FCN can potentially function as a potent anticancer agent against HCC.

Automated summary

In this study, the inhibitory effects of Fangchinoline (FCN) on c-Met, a protein involved in cancer growth and metastasis, were analyzed. FCN was found to inhibit the activation of c-Met and its downstream signals and induce apoptotic cell death. Additionally, FCN suppressed the expression of various oncogenic proteins. In a mouse model, FCN significantly attenuated tumor volume and weight. These findings suggest that FCN could potentially be a potent anticancer agent against hepatocellular carcinoma.