Cytotoxic flavokawain B inhibits the growth and metastasis of hepatocellular carcinoma through the suppression of UCK2-mediated downregulation of the STAT3/Hif-1α/VEGF signalling pathway

Abstract

Hepatocellular carcinoma (HCC) is currently the third most common cancer-related death worldwide. HCC is associated with a high mortality rate due to early recurrence and its distant metastasis to the nearby organs. Current treatment options include surgical removal and transplantation as well as chemotherapy, which remains a major challenge to patient treatment. Flavokawain B (FKB) is a natural bioactive molecule capable of providing effective therapy against this life-threatening disease. This study investigates the effects of Flavokawain B (FKB) on the growth and development of metastatic hepatocellular carcinoma. HepG2 cells were used in this study and a neutral red assay was performed to determine the anti-proliferation effects of FKB at varying concentrations. Cell scratch and exclusion zone assays were performed to assess the inhibitory effects of FKB on cell migration and invasion and relative mRNA levels were quantified using the RT-qPCR. FKB inhibited the proliferation of HepG2 cells at an IC50 value of 28 µM, which conforms to its apoptosis-inducing effects. Cell migration and invasion were significantly inhibited at 7, 14, and 28 µM of FBK. UCK2 expression was significantly downregulated after FKB treatments. Inhibition of STAT3 expression subsequently induced the downregulation of VEGF and HIF-1α expressions. Our data suggest that FKB inhibits HepG2 proliferation and suppresses its metastasis abilities, thus providing a potential alternative and viable strategy against HCC.