Abstract

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