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Perspective

Baffled by Bafilomycin: An Anticancer Agent That Induces Hypoxia-Inducible Factor-1 Expression

Vascular Biology Program, Institute for Cell Engineering; Departments of Pediatrics, Medicine, Oncology, and Radiation Oncology; and McKusick-Nathans Institute of Genetic Medicine, the Johns Hopkins University School of Medicine, Baltimore, Maryland

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) 1 and the cyclin-dependent kinase inhibitor p21^CIP1, a surprising result because HIF-1 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-1 expression leads to increased CIP1 gene expression but does not lead to increased expression of other HIF-1-regulated genes that promote tumor progression.

Address correspondence to: Dr. Gregg L. Semenza, Broadway Research Bldg, Suite 671, 733 N. Broadway, Baltimore, MD 21205

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Bafilomycin Induces the p21-Mediated Growth Inhibition of Cancer Cells under Hypoxic Conditions by Expressing Hypoxia-Inducible Factor-1

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