ascorbic-acid and mequinol

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.

Topics: Animals; Anisoles; Antineoplastic Agents; Ascorbic Acid; Cell Line, Tumor; Cell Proliferation; Cell Survival; Cyclic N-Oxides; Dicumarol; Dithiothreitol; Dose-Response Relationship, Drug; Glutathione; Heptanes; Horseradish Peroxidase; Hydrogen Peroxide; Melanoma, Experimental; Mice; Models, Biological; Monophenol Monooxygenase; NAD; Oxygen; Pyrogallol; Spectrophotometry, Ultraviolet; Spin Labels; Time Factors

Several complicated o-methoxyphenols were oxidized with high selectivity to catechols by a Cu2(+)-ascorbic acid-O2 system. In this way, the RBL-1 5-lipoxygenase inhibitory activities of o-methoxyphenols were greatly increased. [6]-Norgingerol (4), a novel compound derived from [6]-gingerol (3), shows promise as a lead compound for new drugs because of its high inhibitory potency (IC50 = 5.0 x 10(-8) M).

Topics: Anisoles; Arachidonate Lipoxygenases; Ascorbic Acid; Catechols; Chemical Phenomena; Chemistry; Copper; Lipoxygenase Inhibitors; Oxidation-Reduction