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Sakuranetin Induces Melanogenesis in B16BL6 Melanoma Cells through Inhibition of ERK and PI3K/AKT Signaling Pathways
Author(s) -
Drira Riadh,
Sakamoto Kazuichi
Publication year - 2016
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.5606
Subject(s) - phosphorylation , protein kinase b , microphthalmia associated transcription factor , pi3k/akt/mtor pathway , tyrosinase , signal transduction , mapk/erk pathway , downregulation and upregulation , chemistry , kinase , serine , microbiology and biotechnology , biochemistry , biology , gene , enzyme
Sakuranetin (Sak) is considered one of the most important flavanone phytoalexins in regard to antimicrobial activity, and accumulation, in the rice plant. The current study determined that Sak strongly stimulates melanogenesis in B16BL6 melanoma cells in a dose‐dependent manner. This flavonoid upregulates the expression of microphthalmia transcription factor (MITF) and reaches its maximum after 24 h. In addition, Sak was found to increase in vitro tyrosinase ( Tyr ) activity, along with time‐dependent upregulation of Tyr , tyrosinase‐related protein 1 ( TRP1 ), and tyrosinase‐related protein 2 ( TRP2 ). Sakuranetin also decreased the proliferation rate in these cells without directly affecting their viability, as revealed by MTT and trypan blue assays. Further, Sak was shown to inhibit phosphorylation and activation of ERK1/2 from 12 h, without significantly affecting p38 and JNK phosphorylation. Sakuranetin was also found to inhibit the phosphorylation of AKT at threonine 308 and serine 473 and leads to activation of GSK3 β via decreased phosphorylation at serine 9. Taken together, these results demonstrate that Sak stimulates melanogenesis in B16 melanoma cells via inhibition of ERK1/2 and PI3K/AKT signaling pathways, which lead to upregulation of Tyr , TRP1 , and TRP2 . Copyright © 2016 John Wiley & Sons, Ltd.