Baffled by bafilomycin: an anticancer agent that induces hypoxia-inducible factor-1alpha expression.
In an article presented in this issue of Molecular Pharmacology, Lim et al. (p. 1856) investigate the anticancer effect of bafilomycin, an inhibitor of the vacuolar ATPase. The authors report that bafilomycin inhibits cell cycle progression and tumor growth by inducing the expression of hypoxia-inducible factor (HIF) 1alpha and the cyclin-dependent kinase inhibitor p21(CIP1), a surprising result because HIF-1alpha overexpression is associated with tumor growth and angiogenesis in preclinical models and with increased patient mortality in clinical studies. However, the authors demonstrate that bafilomycin-induced HIF-1alpha expression leads to increased CIP1 gene expression but does not lead to increased expression of other HIF-1-regulated genes that promote tumor progression.
Semenza
Gregg L
GL
Vascular Biology Program, Institute for Cell Engineering, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
D000970:Antineoplastic Agents / Q000494:pharmacology*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D018942:Macrolides / Q000494:pharmacology*
D000970:Antineoplastic Agents; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D018942:Macrolides; C057620:bafilomycin A