A research update on the anticancer effects of bufalin and its derivatives.

Bufalin (BF) is a cardiotonic steroid that has recently been found to have substantial anticancer activity; however, more efforts should be directed toward clarifying the detailed molecular mechanisms underlying this activity. BF could exert its anticancer effect by inducing apoptosis in various human cancer cells and thus triggering autophagic cancer cell death. The anti-inflammatory activities of BF are potentially important for its anticancer functions. Notably, some promising synthetic BF derivatives, including poly (ethylene glycol)-based polymeric prodrug of BF and BF211, have shown potent anticancer activity. Additionally, clinical trials regarding the use of BF-related agents in patients have supported the positive effect of BF as an anticancer treatment. Currently, large-scale randomized, double-blind, placebo or positive drug parallel controlled studies are required to confirm the anticancer potential of BF in various cancer types in the clinical setting. The present review will evaluate the potential mechanisms mediated by BF in intracellular signaling events in cancer cells and various promising BF derivatives that may have greater anticancer activity, thereby clarifying BF-mediated anticancer effects. The experimental and clinical results reviewed strongly emphasize the importance of this topic in future investigations.