Arsenic Compounds Arsenic Trioxide and Tetraarsenic Oxide Attenuate 3-Methylcholanthrene-Induced Cytotoxicity in Human Keratinocytes

Abstract

As complex mixtures of carcinogenic metalloids, arsenic compounds have been reported to possess anticytotoxic and antitumor effects. In this study, we evaluated the in vitro protective effects of arsenic compounds tetraarsenic oxide and arsenic trioxide against 3-methylcholanthrene-induced toxicity in human keratinocytes. Human keratinocytes were treated with varying concentrations of arsenic compounds alone or in combination with 3-methylcholanthrene. Treatment with arsenic compounds did not significantly affect cell viability, whereas, 3-methylcholanthrene significantly reduced the viability of human keratinocytes. Furthermore, both tetraarsenic oxide and arsenic trioxide decreased the expression of cytochrome P4501A1 at messenger ribonucleic acid and protein levels in human keratinocytes cells treated with 3-methylcholanthrene. In addition, these arsenic compounds increased the expression of nicotinamide adenine dinucleotide phosphate quinone oxidoreductase 1, which was shown to be inhibited by 3-methylcholanthrene treatment. Together, these findings suggest that tetraarsenic oxide and tetraarsenic oxide significantly inhibit 3-methylcholanthrene-induced cytotoxicity in human keratinocytes by decreasing the expression of cytochrome P4501A1 and increasing the expression of nicotinamide adenine dinucleotide phosphate quinone oxidoreductase 1. Additionally, tetraarsenic oxide was found to be more effective than arsenic trioxide against 3-methylcholanthrene-induced cytotoxicity in vitro.