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OtherPerspective

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

Gregg L. Semenza
Molecular Pharmacology December 2006, 70 (6) 1841-1843; DOI: https://doi.org/10.1124/mol.106.031062
Gregg L. Semenza
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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 p21CIP1, 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.

Footnotes

  • Work in the author's laboratory is supported by grants from the Flight Attendants' Medical Research Institute, National Cancer Institute, National Heart Lung Blood Institute, National Institute of Aging, National Institute of General Medical Sciences, and the American Diabetes Association.

  • Please see the related article on page 1856.

  • ABBREVIATIONS: HIF-1, hypoxia-inducible factor 1; VHL, von Hippel-Lindau protein.

    • Received September 19, 2006.
    • Accepted September 25, 2006.
  • The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 70 (6)
Molecular Pharmacology
Vol. 70, Issue 6
1 Dec 2006
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Baffled by Bafilomycin: An Anticancer Agent That Induces Hypoxia-Inducible Factor-1α Expression

Gregg L. Semenza
Molecular Pharmacology December 1, 2006, 70 (6) 1841-1843; DOI: https://doi.org/10.1124/mol.106.031062

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

Gregg L. Semenza
Molecular Pharmacology December 1, 2006, 70 (6) 1841-1843; DOI: https://doi.org/10.1124/mol.106.031062
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