An Ester Extract of Cochinchina Momordica Seeds Induces Differentiation of Melanoma B16 F1 Cells via MAPKs Signaling

Abstract

Cochinchina momordica seeds (CMS) have been widely used due to antitumor activity by Mongolian tribesof China. However, the details of the underlying mechanisms remain unknown. In the present study, we foundthat an EtOAc (ethyl ester) extract of CMS (CMSEE) induced differentiation and caused growth inhibition ofmelanoma B16 F1 cells. CMSEE at the concentration of 5-200 μg/ml exhibited strongest anti-proliferative effectson B16 F1 cells among other CMS fractions (water or petroleum ether). Moreover, CMSEE induced melanomaB16 F1 cell differentiation, characterized by dendrite-like outgrowth, increasing melanogenesis production, aswell as enhancing tyrosinase activity. Western blot analysis showed that sustained phosphorylation of p38 MAPaccompanied by decrease in ERK1/2 and JNK dephosphorylation were involved in CMSEE-induced B16 F1cell differentiation. Notably, 6 compounds that were isolated and identified may be responsible for inducingdifferentiation of CMSEE. These results indicated that CMSEE contributes to the differentiation of B16 F1 cellsthrough modulating MAPKs activity, which may throw some light on the development of potentially therapeuticstrategies for melanoma treatment.