The induction of P450-mediated oxidation of all-trans retinoic acid by retinoids in head and neck squamous cell carcinoma cell lines.
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 detected 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.
Department of Otolaryngology and Dermatology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
S Y
SY
Kim
I S
IS
Han
H K
HK
Yu
H R
HR
Lee
J W
JW
Chung
J H
JH
Choi
S H
SH
Kim
Y
Y
Byun
T E
TE
Carey
K S
KS
Lee
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000935:Antifungal Agents / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000378:metabolism* / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism*; D003513:Cycloheximide / Q000494:pharmacology; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D003609:Dactinomycin / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D007654:Ketoconazole / Q000494:pharmacology; D010084:Oxidation-Reduction; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012176:Retinoids / Q000378:metabolism*; D014212:Tretinoin / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000903:Antibiotics, Antineoplastic; D000935:Antifungal Agents; D000970:Antineoplastic Agents; D065607:Cytochrome P-450 Enzyme Inhibitors; D011500:Protein Synthesis Inhibitors; D012176:Retinoids; D003609:Dactinomycin; D014212:Tretinoin; D003577:Cytochrome P-450 Enzyme System; D003513:Cycloheximide; D007654:Ketoconazole