Biochemical basis of 4-hydroxyanisole induced cell toxicity towards B16-F0 melanoma cells.

Abstract

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.

• Authors: Majid Y Moridani
• Journal: Cancer letters (Cancer Lett) Vol. 243 Issue 2 Pg. 235-45 (Nov 18 2006) ISSN: 0304-3835 [Print] Ireland
• PMID: 16427188 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anisoles
• Antineoplastic Agents
• Cyclic N-Oxides
• Heptanes
• Spin Labels
• Pyrogallol
• NAD
• mequinol
• Dicumarol
• Hydrogen Peroxide
• Horseradish Peroxidase
• Monophenol Monooxygenase
• Glutathione
• Ascorbic Acid
• Oxygen
• Dithiothreitol
• tempol

Topics

• Animals
• Anisoles (metabolism, pharmacology)
• Antineoplastic Agents (metabolism, pharmacology)
• Ascorbic Acid (metabolism, pharmacology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Cyclic N-Oxides (pharmacology)
• Dicumarol (pharmacology)
• Dithiothreitol (pharmacology)
• Dose-Response Relationship, Drug
• Glutathione (metabolism, pharmacology)
• Heptanes (chemistry, pharmacology)
• Horseradish Peroxidase (metabolism)
• Hydrogen Peroxide (metabolism)
• Melanoma, Experimental (metabolism, pathology)
• Mice
• Models, Biological
• Monophenol Monooxygenase (metabolism)
• NAD (metabolism, pharmacology)
• Oxygen (metabolism)
• Pyrogallol (pharmacology)
• Spectrophotometry, Ultraviolet
• Spin Labels
• Time Factors