Vicenin-2 is a novel inhibitor of STAT3 signaling pathway in human hepatocellular carcinoma

Abstract

We analyzed the potency of vicenin-2, flavanoid present in medicinal herbs such Ocimum sanctum and Moringa oleifera on inhibiting the STAT3 gene expression and its subsequent regulatory genes. We assessed the effect of vicenin-2 against the STAT-3 activation both in the normal and induced stage with IL-6 and EGF. To prove vicenin-2 as a ideal inhibitor of vicenin-2, the STAT3 regulated proteins, protein kinases and phosphatases were also analyzed. The anticancer effect of vicenin-2 was assessed with three different hepatocellular carcinoma cell lines and their effect of induction of apoptosis was assessed with immunoblotting analysis. To confirm the anticancer effect of vicenin-2, the xenografted hepatocellular mice model was treated with vicenin-2 and analyzed for tumor size reduction and apoptotic induction. Vicenin-2 significantly inhibited the STAT3 protein expression even in the presence of IL-6 and EGF induction. Vicenin-2 pretreated cells shown increased phosphorylation of STAT3 protein when treated with pervandate and SHP1-siRNA respectively. Vicenin-2 treatment decreased the expression of STAT3 regulated protein JAK1, JAK2, AKT and also increased the apoptotic proteins procaspase3, PARP. It significantly decreased the levels of antiapoptotic proteins Bcl2, Bclxl, Mcl1, survivig, cell regulatory protein cyclinD1 and angiogenic protein VEGF. In vivo results prove that vicenin-2 potentially inhibits the growth of tumour and induces apoptosis in xenografted hepatocellular mice model. Overall our in vitro and in vivo findings authentically prove that vicenin-2 is a novel STAT-3 inhibitor which imparts anticarcinogenic effect by inhibiting the STAT-3 signaling pathway.

Keywords

• Hepatic cancer
• Vicenin-2
• STAT3 inhibitor
• STAT3 signaling
• In vitro studies
• Xenograft tumour model