Polyphyllin II inhibits liver cancer cells proliferation, migration and invasion through down-regulated cofilin activity and AKT/NF-κB pathway

Abstract

The morbidity and mortality of primary liver cancer is one of the highest among all the cancers. Deficiency of effective treatment and characteristics of cancer metastasis are believed to be responsible for this situation, thus a great demand is required for new agents developing. Polyphyllin II (PP2), an important steroidal saponin extracted from Rhizoma Paris, has emerged as a potential anticancer agent, but the effects of PP2 in liver cancers and its underlying mechanisms remain unexplored. In our study, we found that PP2 could remarkable suppress the proliferation of two liver cancer cell lines--HepG2 and BEL7402 cells, resulting from significant cell death. Besides, low dose of PP2 has displayed the property to inhibit cellular motility and invasion of liver cancer cells. In addition, we have found that PP2-mediated cofilin activity suppression was implicated in the inhibition of liver cancer cells motility. And, decreased expressions of two major hydrolytic enzymes (MMP2/MMP9), through the AKT/NF-κB signaling pathway, may be also responsible for this process. Rescue experiment either done with non-phosphorylatable mutant cofilin-1 (S3A) transfection or an activator of AKT pathway significantly reversed the inhibition effects of PP2 on liver cancer cells. Taken together, we reported a potential agent for liver cancer treatment and revealed its underlying mechanism.