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KMID : 0370220220660050242
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Yakhak Hoeji
2022 Volume.66 No. 5 p.242 ~ p.248
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Involvement of Intracellular Ca2+ and Nitric Oxide in the Hydroxyurea-Induced Melanogenesis
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Lee Yong-Soo
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Abstract
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The molecular mechanism underlying hyperpigmentation as an adverse side effect of the anticancer drug,hydroxyurea (HU), was investigated in B16 melanoma cells. HU increased the melanin content and intracellular Ca2+concentration in a dose-dependent manner. These effects were significantly reduced by treatment with the intracellular Ca2+release blockers, dantrolene and 2-aminoethoxidiphenylborate (2-APB). Additionally, HU induced the production of nitricoxide (NO) in a time- and dose-dependent manner, and this was significantly blocked by inhibitors of the increase inintracellular Ca2+ levels(bis-(o-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid/acetoxymethyl ester, dantrolene, and 2-APB). Furthermore, the HU-induced increases in NO and melanin production were significantly suppressed by NG-nitro-L-arginine methyl ester and 2-(4-carboxy-2-phenyl)-4,4,5,5-tetramethylinidazoline-1-oxyl-3-oxide, an NO synthase inhibitorand an NO scavenger, respectively. These results suggest that HU-induced melanogenesis through NO and an increase inintracellular Ca2+ levels may be involved in the mechanism of its hyperpigmentation effect.
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KEYWORD
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B16 melanoma cell, Hydroxyurea, Hyperpigmentation, Intracellular Ca2+, Melanogenesis, Nitric oxide
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