NAD(P)H:Quinone Oxidoreductase 1 Expression in Human Primary Melanotic Melanomas of the Skin

Abstract

NAD(P)H:quinone oxidoreductase 1 (NQ01; DT-diaphorase; DTD) is a two-electron reducing enzyme which is often over-expressed in cancers and can activate quinones to form cytotoxic species. This over-expression is used as target in the design of novel anti-cancer drugs. DTD is also expressed in normal tissues, but little is known about its "body mapping". Because of the dearth of information on the cell-specific expression of DTD in pigmentproducing cells of the skin, we analysed its expression in normal and tumoral samples. Twenty skin biopsies of primary malignant melanotic melanomas (ten with vertical invasion, ten with superficial spreading) were analysed by immunohistochemistry. In normal skin DTD expression was weak in all epidermal layers, including normal melanocytes. Malignant melanomas showed a very strong DTD expression in tumoral cells of all samples and in endothelial lining of peri-tumoral vessels.These results suggest that DT-diaphorase may be a new marker that could be useful in determining the extent of a malignant melanocytic lesion, and also tend to support the potential of malignant melanomas as target for DTDdirected antitumour agents.

Polyphenols of Salix aegyptiaca modulate the activities of drug metabolizing and antioxidant enzymes, and level of lipid peroxidation

“…DT-Diaphorase also functions as antioxidant enzyme [ 20 ]. Apart from facilitating the two electron reduction of many xenobiotics inducing carcinogenesis [ 38 ], it reduces quinones to prevent the formation of semi quinones and protect from its reactive intermediate metabolites. These findings of the present work suggested that gallic acid and acetylsalicylic acid have a chemopreventive ability and likely to protect against the detrimental effects of toxic compounds.…”