Digoxin and other cardiac glycosides inhibit HIF-1α synthesis and block tumor growth
Proceedings of the National Academy of Sciences, 2008•National Acad Sciences
A library of drugs that are in clinical trials or use was screened for inhibitors of hypoxia-
inducible factor 1 (HIF-1). Twenty drugs inhibited HIF-1-dependent gene transcription by>
88% at a concentration of 0.4 μM. Eleven of these drugs were cardiac glycosides, including
digoxin, ouabain, and proscillaridin A, which inhibited HIF-1α protein synthesis and
expression of HIF-1 target genes in cancer cells. Digoxin administration increased latency
and decreased growth of tumor xenografts, whereas treatment of established tumors …
inducible factor 1 (HIF-1). Twenty drugs inhibited HIF-1-dependent gene transcription by>
88% at a concentration of 0.4 μM. Eleven of these drugs were cardiac glycosides, including
digoxin, ouabain, and proscillaridin A, which inhibited HIF-1α protein synthesis and
expression of HIF-1 target genes in cancer cells. Digoxin administration increased latency
and decreased growth of tumor xenografts, whereas treatment of established tumors …
A library of drugs that are in clinical trials or use was screened for inhibitors of hypoxia-inducible factor 1 (HIF-1). Twenty drugs inhibited HIF-1-dependent gene transcription by >88% at a concentration of 0.4 μM. Eleven of these drugs were cardiac glycosides, including digoxin, ouabain, and proscillaridin A, which inhibited HIF-1α protein synthesis and expression of HIF-1 target genes in cancer cells. Digoxin administration increased latency and decreased growth of tumor xenografts, whereas treatment of established tumors resulted in growth arrest within one week. Enforced expression of HIF-1α by transfection was not inhibited by digoxin, and xenografts derived from these cells were resistant to the anti-tumor effects of digoxin, demonstrating that HIF-1 is a critical target of digoxin for cancer therapy.
National Acad Sciences