bufalin

Bufalin is a cardiotonic steroid and a bufadienolide toxin originally isolated from the venom of Chinese toads (Bufo species), notably Bufo gargarizans. It is an active ingredient in the traditional Chinese medicine ChanSu and Huachansu. Bufalin acts primarily as a potent inhibitor of Na+/K+-ATPase (sodium-potassium ATPase), binding to its α1, α2, and α3 subunits with nanomolar affinity. This inhibition leads to increased intracellular sodium and calcium concentrations in cardiac cells—underlying its cardiotonic effects—and also triggers apoptosis in various cancer cell lines via mitochondria-mediated pathways involving p53 activation and modulation of pro-apoptotic/anti-apoptotic proteins such as Bax and Bcl‑2. Bufalin has demonstrated antineoplastic activity in vitro against multiple tumor types (e.g., hepatocellular carcinoma, lung carcinoma) by inducing apoptosis or necroptosis through mechanisms that include DNA damage response (γ-H2AX upregulation), reactive oxygen species generation (RIP1–ROS axis), MAPK pathway activation (AP‑1 transcription factor), JNK stimulation, topoisomerase II reduction, and downregulation of exportin 1/XPO1. Despite promising preclinical anticancer effects—including activity against drug-resistant cancer cell lines—its clinical development is limited by significant cardiotoxicity[2][3][4][5][6][7].

Other names

bufalin3beta,14beta-dihydroxy-5beta-bufa-20,22-dienolide3-beta,14-dihydroxy-5-beta-bufa-20,22-dienolide3,14-dihydroxy-bufa-20,22-dienolide