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J Dermatol Sci ; 79(1): 74-83, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25869056

ABSTRACT

BACKGROUND: Tyrosinase (TYR) is the key enzyme controlling the production of melanin. Very few papers have reported that andrographolide can inhibit melanin content. OBJECTIVE: To investigate the effects of andrographolide on melanin synthesis. METHODS: Cell viability, melanin content, TYR activity, transcriptional and protein expression levels of TYR family and other kinds of proteins involved in melanogenesis were measured after the treatments of andrographolide. RESULTS: It was found that andrographolide decreased melanin content, TYR activity and transcriptional and protein expression of TYR family and microphthalmia-associated transcription factor (MITF) in B16F10 melanoma cells. Data showed andrographolide also decreased melanin content and TYR content in ultraviolet B (UVB) irradiation induced brown guinea pigs. Moreover, we found that melanin content and TYR activity were effectively inhibited in Human Epidermis Melanocyte (HEM) treated with andrographolide at the medium concentrations without apparent effect on cell viability. Results in experiments treated with MG-132 or cycloheximide (CHX) showed that andrographolide lowered the content of ß-catenin in cell nucleus resulting from accelerating the degradation of ß-catenin. Phosphorylation of glycogen synthase kinase 3ß (GSK3ß) and Akt decreased simultaneously. 6-Bromoindirubin-3'-oxime (BIO, inhibitor of GSK3ß) and insulin-like growth factors-1 (IGF-1, activator of Akt) could reverse the decline of ß-catenin in B16F10 cells induced by andrographolide. CONCLUSION: These results demonstrate that andrographolide can effectively suppress melanin content and TYR activity in B16F10 cells, HEM cells and UVB-induced brown guinea pig skin by decreasing phosphorylation of GSK3ß dependent on Akt, promoting the degradation of ß-catenin, inhibiting ß-catenin into the nucleus and decreasing the expression of MITF and TYR family. Data indicate that andrographolide may be a potential whiting agent which can have great market in cosmetics and in clinical such as curing hyperpigmentation disorders.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Diterpenes/pharmacology , Melanins/biosynthesis , Melanoma, Experimental/enzymology , Protein Biosynthesis/drug effects , Wnt Signaling Pathway/drug effects , Animals , Cell Line, Tumor , Cell Survival , Glycogen Synthase Kinase 3/metabolism , Glycogen Synthase Kinase 3 beta , Guinea Pigs , Humans , Melanocytes , Melanoma, Experimental/genetics , Melanoma, Experimental/metabolism , Microphthalmia-Associated Transcription Factor/genetics , Microphthalmia-Associated Transcription Factor/metabolism , Monophenol Monooxygenase/metabolism , Protein Biosynthesis/radiation effects , Proto-Oncogene Proteins c-akt/metabolism , Ultraviolet Rays , beta Catenin/metabolism
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