期刊
ONCOTARGET
卷 8, 期 34, 页码 56868-56879出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.18097
关键词
oleoylethanolamide; melanin; tyrosinase; alpha-melanocyte stimulating hormone; B16 mouse melanoma cell
资金
- Natural Science Foundation of Fujian, China [2016J01415, 2016D024]
The present study aimed to examine the potential inhibitory activity of oleoylethanolamide (OEA) on alpha-melanocyte stimulating hormone (alpha-MSH)-stimulated melanogenesis and the molecular mechanism(s) involved in the process in B16 mouse melanoma cells. Our data demonstrated that OEA markedly inhibited melanin synthesis and tyrosinase activity in alpha-MSH-stimulated B16 cells. In addition, the expression of melanogenesis-related proteins, such as melanocortin-1 receptor (MC1R), microphthalmia-associated transcription factor (MITF), tyrosinase-related protein-1 (TRP-1) and tyrosinase, was suppressed in a concentration-dependent manner by OEA. In addition, OEA may suppress melanogenesis through a peroxisome proliferator-activated receptor a (PPAR alpha)-independent pathway. Moreover, OEA activated ERK, Akt, p38 pathways and inhibits CREB pathway in a-MSH-stimulated B16 cells. The specific ERK inhibitor PD98059 partly blocked OEA-inhibited melanin synthesis and tyrosinase activity and partly abrogated the OEA-suppressed expression of melanogenic proteins. Furthermore, OEA presented remarkable inhibition on the body pigmentation in the zebrafish model system. Our findings demonstrated that OEA is an effective inhibitor of hyperpigmentation through activation of ERK, Akt and p38 pathways, inhibition of the CREB pathway, and subsequent down-regulation of MITF, TRP-1 and tyrosinase production.
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