Intracellular oxidation of methyl p-coumarate is involved in anti-melanogenic and cytotoxic activities against melanoma cells

Abstract

Tyrosinase-catalyzed L -tyrosine oxidation is a key step in melanogenesis, and intense melanin formation is often a problem in chemotherapies or food preservation. Methyl p -coumarate is isolated from fresh flower of medicinal plant, Trixis michuacana var longifolia (D. Dow) C., and it suppressed melanogenesis in cultured murine B16-F10 melanoma cells while p -coumaric acid did not show anti-melanogenic activity. Methyl p -coumarate exhibited cytotoxicity with an IC 50 of 130 μM (23.2 µg/mL), and p -coumaric acid showed similar activity, but to a lesser extent, suggesting that the anti-melanogenic activity of methyl p -coumarate is at least due to the melanocytotoxicity. This cytotoxicity of methyl p -coumarate was reduced in a dose-dependent manner by ascorbic acid but not with butylated hydroxyanisole. Moreover, methyl 4-methoxycinnamate, which lacks the oxidizable phenolic hydroxyl group, still exhibited comparable cytotoxicity to methyl p -coumarate. In addition, anethole did not show noticeable cytotoxicity, indicating that the enone moiety is an essential element in eliciting melanocytotoxicity. Thus, the enone moiety in methyl p -coumarate is a biologically critical nucleophilic group as a Michael reaction acceptor contributing to the anti-melanogenic activity and cytotoxicity against melanoma cells. • Methyl p -coumarate inhabits melanogenesis in cultured murine B16-F10 melanoma cells. • Cytotoxicity of methyl p -coumarate was restored with vitamin C but not with BHA. • Enone moiety of methyl p -coumarate is an important as a Michael reaction acceptor.