Effects of Quercetin on Mushroom Tyrosinase and B16-F10 Melanoma Cells.docVIP

Molecules 2007, 12, 1045-1056 molecules ISSN 1420-3049 ? 2007 by MDPI /molecules Full Paper Effects of Quercetin on Mushroom Tyrosinase and B16-F10 Melanoma Cells Isao Kubo*, Teruhiko Nitoda and Ken-ichi Nihei Department of Environmental Science, Policy and Management, University of California, Berkeley, CA 94720-3114, USA * Author to whom correspondence should be addressed; E-mail: ikubo@ Received: 12 April 2007; in revised form: 14 May 2007 / Accepted: 14 May 2007 / Published: 15 May 2007 Abstract: In searching for tyrosinase inhibitors from plants using L-3,4-dihydroxyphenylalanine (L-DOPA) as a substrate, quercetin was found to be partially oxidized to the corresponding o-quinone under catalysis by mushroom tyrosinase (EC ). Simultaneously, L-DOPA was also oxidized to dopaquinone and both o-quinones were further oxidized, respectively. The remaining quercetin partially formed adducts with dopaquinone through a Michael type addition. In general, flavonols form adducts with dopaquinone as long as their 3-hydroxyl group is free. Quercetin enhanced melanin production per cell in cultured murine B16-F10 melanoma cells, but this effect may be due in part to melanocytotoxicity. The concentration leading to 50% viable cells lost was established as 20 μM and almost complete lethality was observed at 80 μM. Keywords: Quercetin, mushroom tyrosinase, adducts, murine B16-F10 melanoma cells, cytotoxicity Introduction The oxidation of L-tyrosine to melanin catalyzed by tyrosinase is of considerable importance since melanin has many functions in human systems. Alterations in melanin synthesis occur in many disease states. Melanins play a crucial role in the absorption of free radicals generated within the cytoplasm and in shielding the host from various types of ionizing radiation. The hydroxylation of  Molecules 2007, 12 1046 L-tyrosine, the initial step in melanin synthesis [