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http://dx.doi.org/10.15230/SCSK.2021.47.2.107

Melanogenesis Promotion by 3-Deazaneplanocin A, a Specific Inhibitor of S-Adenosylhomocysteine Hydrolase, in B16/F10 Melanoma Cells  

Hwang, Yun Jeong (Department of Molecular Medicine, School of Medicine, Brain Korea (BK) 21 Plus Kyungpook National University (KNU) Biomedical Convergence Program, Cell and Matrix Research Institute, Kyungpook National University)
Boo, Yong Chool (Department of Molecular Medicine, School of Medicine, Brain Korea (BK) 21 Plus Kyungpook National University (KNU) Biomedical Convergence Program, Cell and Matrix Research Institute, Kyungpook National University)
Publication Information
Journal of the Society of Cosmetic Scientists of Korea / v.47, no.2, 2021 , pp. 107-121 More about this Journal
Abstract
Skin hypopigmentation, which is observed in albinism or vitiligo, occurs when melanin synthesis is decreased by genetic, epigenetic, and other factors. To identify drug candidates that can promote melanin synthesis in cells, we screened an epigenetic modulator library consisting of 141 cell-permeable, small molecule drugs. B16/F10 murine melanoma cells were treated with each drug at 0.1 𝜇M and melanin synthesis and cell viability were subsequently monitored. As a result, (-)-neplanocin A, 3-deazaneplanocin A (DZNep), and DZNep hydrochloride were found to increase cellular melanin synthesis without causing cytotoxicity. Because these three structurally related drugs exhibited similar dose-dependent effects on melanin synthesis and cell viability, DZNep was selected as a representative drug for additional experiments. DZNep increased intracellular melanin content and tyrosinase (TYR) activity. DZNep also induced the expression of TYR, tyrosinase-related protein 1 (TYRP1), and dopachrome tautomerase (DCT) at the mRNA and protein levels. DZNep also induced the mRNA and protein expression of microphthalmia-associated transcription factor (MITF), a key regulator of melanin synthesis. DZNep is a specific inhibitor of S-adenosylhomocysteine hydrolase and it caused the accumulation of S-adenosylhomocysteine that inhibits histone methyltransferases in cells. This study suggests that melanogenesis can be modulated by targeting S-adenosylhomocysteine hydrolase in certain cellular contexts.
Keywords
promelanogenic; 3-deazaneplanocin A; epigenetic; histone methyltransferase; S-adenosylhomocysteine hydrolase;
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