Riccardin D-26, a synthesized macrocyclic bisbibenzyl compound, inhibits human hepatocellular carcinoma growth through induction of apoptosis in p53-dependent way

Riccardin D-26 is a synthesized macrocyclic bisbibenzyl compound. We investigated the effect of Riccardin D-26 on human hepatocellular carcinomas. Riccardin D-26 possessed stronger activity against SMMC-7721 cells than human normal liver cells. Riccardin D-26 injection effectively delayed the growth of SMMC-7721 xenografts in mice without significant toxicity. This effect of Riccardin D-26 was associated with the status of p53 and its targets, bax and p21Waf1/Cip1. Riccardin D-26 activated p53 expression and induced cancer cells to apoptosis through the p53-mediated transcription-dependent and -independent pathway. Overall, Riccardin D-26 may inhibit hepatocellular carcinoma growth through induction of apoptosis in p53-dependent pathway.

► Riccardin D-26 inhibited p-53 wild cancer cells more strongly than p-53 reduced cells.
► Riccardin D-26 exhibited less inhibition towards normal liver cells in vitro.
► Riccardin D-26 exhibited insignificant toxicity in vivo.
► The inhibition of Riccardin D-26 in vitro and in vivo was due to induction of apoptosis.
► Riccardin D-26 exerted inhibitory effects via p-53 dependent way.