Volume 47, Issue 8 , Pages 955-958, August 1998
The induction of P450-mediated oxidation of all-trans retinoic acid by retinoids in head and neck squamous cell carcinoma cell lines☆☆☆
Abstract
All-trans retinoic acid (RA) can be catabolized into polar metabolites by cytochrome P450 (P450) in several tissues including the skin. We examined eight different squamous cell carcinoma (SCC) cell lines to determine their capacity to induce P450-mediated oxidation of RA. Among the eight different cell lines, enhanced catabolism was detectd in AMC-HN-1, -2, -5, and -6, whereas it was not found in the cell lines of AMC-HN-3, -4, -7, and -8. It was found that the enhanced catabolism brought on by P450 induction was blocked when RA was added to AMC-HN-6 along with actinomycin D or cyclohexamide. Also, this catabolism was inhibited by ketoconazole. P450-mediated oxidation was detectable within 4 hours of RA treatment, and RA catabolism reached its maximum 16 hours after treatment. P450 was induced by 13-cis-RA, 9-cis-RA, and retinal; however, retinol could not induce P450. In conclusion, P450 can be induced by retinoids in head and neck SCC (HNSCC) cells and the ability of retinoids to induce P450 can serve as an important factor in determining the biological effect of retinoids.
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☆ Supported by Grant No. HMP-96-G-32 from the 1996 Highly Advanced National Projects on the development of Biomedical Engineering and Technology, Ministry of Health and Welfare, Republic of Korea.
☆☆ Drs Kim and Han are equal contributors as first author.
PII: S0026-0495(98)90350-X
© 1998 Published by Elsevier Inc.
Volume 47, Issue 8 , Pages 955-958, August 1998
