(−)-Curine induces cell cycle arrest and cell death in hepatocellular carcinoma cells in a p53-independent way

Abstract Hepatocellular carcinoma(HCC) is one of the most common malignancies worldwide, however, drug resistance is still a tough problem of it. As in many other cancers, p53 mutations are commonly observed in HCCs (Hussain et al., 2007; Levine et al., 1994) [1] , [2] . Tumor tissues with mutant p53 seems to be more aggressive and resist to chemotherapy than that harboring wide-type p53 (Harris and Hollstein, 1994; Parrales and Iwakuma, 2015) [3] , [4] . (−)-Curine, a novel bisbenzylisoquinoline alkaloid, is one of the main components isolated from the roots of Cyclea wattii . Here, it was found to exert cytotoxity on hepatocellular carcinoma (HCC) cells regardless of p53 status. We found that (−)-curine induced G1 arrest and cell death in HepG2 cells with wild-type p53 as well as Huh-7 cells with mutant p53. In HepG2 cells, knocking down of p53 did not change its cellular responses to (−)-curine, and same degree of G1 arrest and cell death were occurred after p53 knockdown. Taken together, our data demonstrate that (−)-curine can inhibit viability of hepatocellular carcinoma cells in regardless of p53 status. It shed light on new therapy methods for HCC.