Nicotinamide inhibits the early stage of carcinogen‐induced hepatocarcinogenesis in mice and suppresses human hepatocellular carcinoma cell growth

Hepatocellular carcinoma (HCC) can cause severe complications, resulting in a high incidence of recurrence after treatment of the primary tumor. Recently, we have shown that nicotinamide effectively inhibits the growth and progression of bladder tumors by up-regulating RUNX3 and p300 expression. Therefore, in this study, the efficacy and inhibitory mechanisms of nicotinamide against HCC were investigated in mice and HCC cell lines, respectively. To evaluate the inhibitory effects of nicotinamide on HCC development, mice were injected with diethylnitrosamine (DEN) and simultaneously treated with 1% nicotinamide. Also, the effect of nicotinamide on human HCC cell lines was assessed by measuring caspase activity, cell proliferation, and DNA content using immunoblot analysis and reverse-transcriptase polymerase chain reaction. It was found that nicotinamide significantly inhibited the development of pre-neoplastic lesions (foci and adenomas) during the early stages of HCC. Furthermore, nicotinamide inhibited cell proliferation and induced mitochondria-mediated apoptosis in HCC cell lines. It also increased the expression of p21, and the expression and acetylation of p53. These results strongly suggest that nicotinamide inhibits the progression of early-stage HCC and may contribute to the induction of apoptosis and the inhibition of proliferation of HCC cells. Taken together, the results of this study indicate that nicotinamide is a potential chemopreventive agent, i.e., it may prevent the progression of early HCC development and/or the recurrence of HCC after primary treatment.