Curcumin suppresses alpha-melanocyte stimulating hormone-stimulated melanogenesis in B16F10 cells.
The present study was designed to assess the potential inhibitory activity of curcumin on the alpha-melanocyte stimulating hormone (alpha-MSH)-stimulated melanogenesis signal pathway in B16F10 melanoma cells. The molecular mechanism of curcumin-induced inhibitory activity on the alpha-MSH-stimulated melanogenesis signal pathway, including expression of melanogenesis-related proteins and activation of melanogenesis-regulating proteins, was examined in B16F10 cells. Curcumin suppressed the cellular melanin contents and the tyrosinase activity in alpha-MSH-stimulated B16F10 cells. In addition, the expression of melanogenesis-related proteins such as microphthalmia-associated transcription factor (MITF), tyrosinase, and tyrosinase-related protein 1 and 2 was suppressed by curcumin in the alpha-MSH-stimulated B16F10 cells. Notably, a melanogenesis-regulating signal such as mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) or phosphatidylinositol 3-kinase (PI3K)/Akt was activated by curcumin in the B16F10 cells treated with or without alpha-MSH. The suppressive activity of curcumin on alpha-MSH-induced melanogenesis was down-regulated by PD98059 and by LY294002. Our results suggest that the suppressive activity of curcumin on alpha-MSH-stimulated melanogenesis may involve the down-regulation of MITF and its downstream signal pathway through the activation of MEK/ERK or PI3K/Akt.
Lee
Jun-Hyuk
JH
Chemistry and Biotechnology Examination Bureau, Korean Intellectual Property Office, Daejeon 302-701, Korea.
Jang
Ji-Yeon
JY
Park
Cheol
C
Kim
Byung-Woo
BW
Choi
Yung-Hyun
YH
Choi
Byung-Tae
BT
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D003474:Curcumin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D008543:Melanins / Q000378:metabolism*; D008545:Melanoma / Q000378:metabolism / Q000473:pathology; D051739:Microphthalmia-Associated Transcription Factor / Q000378:metabolism; D014442:Monophenol Monooxygenase / Q000378:metabolism*; D009025:Morpholines / Q000494:pharmacology; D010088:Oxidoreductases / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000521:alpha-MSH / Q000494:pharmacology*
D000970:Antineoplastic Agents; D002867:Chromones; D003474:Curcumin; D004791:Enzyme Inhibitors; D048049:Extracellular Signal-Regulated MAP Kinases; D005419:Flavonoids; D008543:Melanins; D051739:Microphthalmia-Associated Transcription Factor; D014442:Monophenol Monooxygenase; D009025:Morpholines; D010088:Oxidoreductases; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D000521:alpha-MSH; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C064056:tyrosinase-related protein-1; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one