This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Forgue-Lafitte, M.-E. Articles by Mester, J. Search for Related Content PubMed PubMed Citation Articles by Forgue-Lafitte, M.-E. Articles by Mester, J.

Effects of Ketoconazole on the Proliferation and Cell Cycle of Human Cancer Cell Lines¹

Institut National de la Santé et de la Recherche Médicale, INSERM U 55, Centre de Recherches Paris-Saint-Antoine, Hôpital Saint-Antoine, 184 Faubourg Saint-Antoine, 75012 Paris, France

² To whom requests for reprints should be addressed.

The growth-inhibitory effects of ketoconazole, an antifungal agent which inhibits arachidonic acid lipoxygenases and cytochrome P-450 enzymes, were tested in human colon and breast cancer cell lines. In the serum independent HT29-S-B6 colon cell clone, ketoconazole reduced cell proliferation and [³H]thymidine incorporation in a dose-dependent fashion, with a 50% inhibitory concentration of approximately 2.5 µM. Flow cytometry showed an accumulation of cells in the G₀-G₁ phase of the cell cycle and a concomitant decrease of the percentage of cells in S phase. Ketoconazole also inhibited [³H]thymidine incorporation in the hormone-independent breast cancer cells MDA-MB-231 and Evsa-T, with respective 50% inhibitory concentrations of approximately 13 and 2 µM. The mechanism of action of ketoconazole is unknown. However, another lipoxygenase inhibitor, BW755C, inhibited only weakly [³H]thymidine incorporation and accumulated the cells in S and G₂. Conversely, clotrimazole and SKF525A, inhibitors of cytochrome P-450 enzymes, had effects similar to those of ketoconazole on HT29-S-B6 cells whereas metronidazole and secnidazole, other azole derivatives which do not inhibit cytochrome P-450 enzymes, had no effect. The results suggest that cytochrome P-450 enzyme(s) activity(ies) could be implicated in the antiproliferative effects of ketoconazole.

¹ This work was supported by INSERM.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 6/ 8/92. Accepted 10/ 2/92.

This article has been cited by other articles:

				J. MARTÍNEZ-BOTAS, Y. SUÁREZ, A. J. FERRUELO, D. GÓMEZ-CORONADO, and M. A. LASUNCIÓN Cholesterol starvation decreases P34cdc2 kinase activity and arrests the cell cycle at G2 FASEB J, August 1, 1999; 13(11): 1359 - 1370. [Abstract] [Full Text]