title: 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 tribes of China. However, the details of the underlying mechanisms remain unknown. In the present study, we found that an EtOAc (ethyl ester) extract of CMS (CMSEE) induced differentiation and caused growth inhibition of melanoma B16 F1 cells. CMSEE at the concentration of 5-200 μg/ml exhibited strongest anti-proliferative effects on B16 F1 cells among other CMS fractions (water or petroleum ether). Moreover, CMSEE induced melanoma B16 F1 cell differentiation, characterized by dendrite-like outgrowth, increasing melanogenesis production, as well as enhancing tyrosinase activity. Western blot analysis showed that sustained phosphorylation of p38 MAP accompanied by decrease in ERK1/2 and JNK dephosphorylation were involved in CMSEE-induced B16 F1 cell differentiation. Notably, 6 compounds that were isolated and identified may be responsible for inducing differentiation of CMSEE. These results indicated that CMSEE contributes to the differentiation of B16 F1 cells through modulating MAPKs activity, which may throw some light on the development of potentially therapeutic strategies for melanoma treatment.
authors.affiliation: Research Centre, Fourth Hospital of Hebei Medical University, Hebei, China.
authors.forename: Lian-Mei
authors.initials: LM
authors.lastname: Zhao
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Han
authors.forename: Feng-Zhi
authors.initials: FZ
authors.lastname: Ren
authors.forename: Shu-Hong
authors.initials: SH
authors.lastname: Chen
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Liu
authors.forename: Ming-Xia
authors.initials: MX
authors.lastname: Wang
authors.forename: Mei-Xiang
authors.initials: MX
authors.lastname: Sang
authors.forename: Bao-En
authors.initials: BE
authors.lastname: Shan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D004952:Esters / Q000737:chemistry; D005434:Flow Cytometry; D048670:MAP Kinase Kinase 4 / Q000378:metabolism*; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D015394:Molecular Structure; D029775:Momordica / Q000737:chemistry*; D014442:Monophenol Monooxygenase / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology; D012639:Seeds / Q000737:chemistry*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
chemical_list: D004952:Esters; D010936:Plant Extracts; D014442:Monophenol Monooxygenase; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048670:MAP Kinase Kinase 4