BF211, a derivative of bufalin, enhances the cytocidal effects in multiple myeloma cells by inhibiting the IL-6/JAK2/STAT3 pathway.

Despite remarkable advances in multiple myeloma (MM) therapy, this condition remains incurable. BF211 is an active compound derived from bufalin, which is isolated from the Traditional Chinese Medicine, Chansu. In this study, we explored the cytotoxicity of BF211 in 20 tumor cell lines and discovered that the MM cell lines, ARP-1 and CAG, exhibited greater sensitivity to BF211. Compared with bufalin, BF211 induced a greater apoptotic effect and lower acute toxicity at nanomolar concentration. The IL-6/JAK2/STAT3 signaling pathway is essential to the progression and development of MM. We showed that exogenous IL-6 promoted MM cell proliferation in a dose-dependent manner and this effect was blocked by BF211. Furthermore, BF211 suppressed the phosphorylation of JAK2 and STAT3 both in vivo and in vitro. In a mouse MM xenograft model, BF211 significantly inhibited tumor growth and did not affect body weight. In conclusion, the anti-MM activity of BF211 is mediated mainly by suppressing the IL-6/JAK2/STAT3 signaling pathway. Thus, we suggest that BF211 warrants further investigation in clinical trials in MM.