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/O₂. 4-HA metabolism by horseradish peroxidase/H₂O₂ 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.

Keywords: 4-Hydroxyanisole, Tyrosinase, Melanoma, B16, B16-F0, Anticancer drugs, Cancer, Alkoxyphenols, Phenol, Catechols, Toxicity