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Aim of the review  In the past decade, increasing research attention investigated the novel therapeutic potential of steroidal cardiac glycosides in cancer treatment. Huachansu and its main active constituent Bufalin have been studied in vitro, in vivo and clinical studies. This review aims to summarize the multi-target and multi-pathway pharmacological effects of Bufalin and Huachansu in the last decade, with the aim of providing a more comprehensive view and highlighting the recently discovered molecular mechanisms.    Results  Huachansu and its major derivative, Bufalin, had been found to possess anti-cancer effects in a variety of cancer cell lines both in vitro and in vivo. The underlying anti-cancer molecular mechanisms mainly involved anti-proliferation, apoptosis induction, anti-metastasis, anti-angiogenesis, epithelial–mesenchymal transition inhibition, anti-inflammation, Na + /K + -ATPase activity targeting, the steroid receptor coactivator family inhibitions, etc. Moreover, the potential side-effects and toxicities of the toad extract, Huachansu, and Bufalin, including hematological, gastrointestinal, mucocutaneous and cardiovascular adverse reactions, were reported in animal studies and clinic trails.    Conclusions  Further research is needed to elucidate the potential drug–drug interactions and multi-target interaction of Bufalin and Huachansu. Large-scale clinical trials are warranted to translate the knowledge of the anticancer actions of Bufalin and Huachansu into clinical applications as effective and safe treatment options for cancer patients in the future.

New therapeutic aspects of steroidal cardiac glycosides: the anticancer properties of Huachansu and its main active constituent Bufalin