title: Proton pump inhibitors decrease melanogenesis in melanocytes.
abstract: Proton pump inhibitors (PPIs) are widely used as inhibitors of gastric juice secretion for treatment of gastroesophageal reflux disease. However, there are no previous studies of the effects on melanogenesis resulting from PPI treatments. Therefore, the aim of the present study was to investigate the effects of PPIs on melanogenesis in melan-a cells derived from immortalized mouse melanocytes. Tyrosinase activity and copper-chelating activity were measured spectrophotometrically. In addition, the melanin content and viability of melan-a cells treated with PPIs were assessed and the mRNA levels of melanogenesis-associated genes were measured by reverse transcription-polymerase chain reaction. Treatment with rabeprazole, but not the other PPIs tested, resulted in strong, dose-dependent inhibition of mushroom tyrosinase (TYR). By contrast, each of the PPIs tested exhibited copper-chelating activity. Treatment of melan-a cells with 100 µM concentrations of the PPIs resulted in significantly reduced melanin synthesis and reduced expression of several melanogenesis-associated genes, includingTYR, TYR-related protein-1 (TRP-1) andTRP-2, and microphthalmia-associated transcription factor, but did not result in cytotoxic effects. These results suggest that PPIs inhibit melanin biosynthesis in melan-a cells via the downregulation of melanogenesis-associated genes. Furthermore, the findings indicate that PPIs in general could be utilized as skin-whitening agents and/or as biomaterial for treating hyperpigmentation disorders.
authors.affiliation: Department of Food Science and Biotechnology, Kyungpook National University, Daegu 702-701, Republic of Korea.
authors.forename: Seung-Hwa
authors.initials: SH
authors.lastname: Baek
authors.affiliation: Department of Food Science and Biotechnology, Kyungpook National University, Daegu 702-701, Republic of Korea ; Department of Nano-Science and Technology, Kyungpook National University, Daegu 702-701, Republic of Korea.
authors.forename: Sang-Han
authors.initials: SH
authors.lastname: Lee
keywords: anti-melanogenic effects; melanocyte; melanogenesis-associated genes; proton pump inhibitors; tyrosinase