Inhibitory effects of generic drug homochlorcyclizine on melanogenesis in mouse B16 melanoma cells

• Main Authors: Chin-tsun Chen, 陳金村
• Other Authors: Te-sheng Chang
• Format: Others
• Language: zh-TW
• Published: 2011
• Online Access: http://ndltd.ncl.edu.tw/handle/28666315023974693040

碩士 === 國立臺南大學 === 生物科技學系碩士班 === 99 === The histamine receptor H1 antagonist homochlorcyclizine (HC) has been widely used as an antihistamine agent for the treatment of allergies. However, the effect of HC on skin pigmentation is not known. In the present study, we investigated the inhibitory effect of HC on melanogenesis in mouse B16 melanoma cells. Our results showed that HC inhibited melanogenesis in B16 cells stimulated with either α-melanocyte stimulating hormone (α-MSH) or 3-isobutyl-1-methylxanthin (IBMX) in a dose-dependent manner, and it did not result in cytotoxicity. Further, the inhibitory activity of HC was over 50-fold stronger than that of arbutin, a well-known skin-whitening agent. In addition, melanogenesis inhibition by HC was not quenched by another H1 antagonist, hydroxyzine, and melanogenesis was not inhibited by other histamine receptor antagonists. Surprisingly, despite the strong inhibition of melanogenesis by HC in B16 cells, HC did not inhibit tyrosinase activity in both cell-based and cell-free systems. Neither crude cellular tyrosinase activity nor melanosome-enriched tyrosinase activity was inhibited in the HC-treated cells. In addition, HC also did not directly inhibit the enzyme activity of either crude murine tyrosinase or commercial mushroom tyrosinase. Finally, western blotting and reverse-transcription polymerase chain reaction (RT-PCR) were performed, and it was confirmed that both tyrosinase and its mRNA were not downregulated by HC in α-MSH-stimulated B16 cells. These results suggested that HC inhibited melanogenesis of B16 cells by a mechanism other than reduction of the cellular tyrosinase activity. From the present study, HC was proven to be a good candidate as a skin-whitening agent for treatment of skin hyperpigmentation, and this generic drug might be suitable for use in combination with other depigmenting agents due to its unique inhibition mechanism.