Biochemical basis of 4-hydroxyanisole induced cell toxicity towards B16-F0 melanoma cells.
In the current work we investigated for the first time the biochemical basis of 4-hydroxyanisole (4-HA) induced toxicity in B16-F0 melanoma cells. It was found that dicoumarol, a diaphorase inhibitor, and 1-bromoheptane, a GSH depleting agent, increased 4-HA induced toxicity towards B16-F0 cells whereas dithiothreitol, a thiol containing agent, and ascorbic acid (AA), a reducing agent, largely prevented 4-HA toxicity. TEMPOL and pyrogallol, free radical scavengers, did not significantly prevent 4-HA toxicity towards B16-F0 cells. GSH>AA>NADH prevented the o-quinone formation when 4-HA was metabolized by tyrosinase/O(2). 4-HA metabolism by horseradish peroxidase/H(2)O(2) was prevented more effectively by AA than NADH>GSH. We therefore concluded that quinone formation was the major pathway for 4-HA induced toxicity in B16-F0 melanoma cells whereas free radical formation played a negligible role in the 4-HA induced toxicity.
Moridani
Majid Y
MY
Department of Pharmaceutical Sciences, School of Pharmacy, and Department of Pediatrics, School of Medicine, Texas Tech University Health Sciences Center, 1300 Coulter Drive, Amarillo, TX 79106, USA. majid.moridani@ttuhsc.edu <majid.moridani@ttuhsc.edu>
D000818:Animals; D000840:Anisoles / Q000378:metabolism / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology; D001205:Ascorbic Acid / Q000378:metabolism / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D003497:Cyclic N-Oxides / Q000494:pharmacology; D001728:Dicumarol / Q000494:pharmacology; D004229:Dithiothreitol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism / Q000494:pharmacology; D006536:Heptanes / Q000737:chemistry / Q000494:pharmacology; D006735:Horseradish Peroxidase / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D008546:Melanoma, Experimental / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008954:Models, Biological; D014442:Monophenol Monooxygenase / Q000378:metabolism; D009243:NAD / Q000378:metabolism / Q000494:pharmacology; D010100:Oxygen / Q000378:metabolism; D011748:Pyrogallol / Q000494:pharmacology; D013056:Spectrophotometry, Ultraviolet; D013113:Spin Labels; D013997:Time Factors
D000840:Anisoles; D000970:Antineoplastic Agents; D003497:Cyclic N-Oxides; D006536:Heptanes; D013113:Spin Labels; D011748:Pyrogallol; D009243:NAD; C009760:mequinol; D001728:Dicumarol; D006861:Hydrogen Peroxide; D006735:Horseradish Peroxidase; D014442:Monophenol Monooxygenase; D005978:Glutathione; D001205:Ascorbic Acid; D010100:Oxygen; D004229:Dithiothreitol; C001803:tempol