ABSTRACT
Sodium 2-mercaptoethanesulfonate (mesna) is a protective agent that is widely used in medicine because of its antioxidant effects. Recently, reactive oxygen species (ROS) were shown to increase pigmentation. Thus, ROS scavengers and inhibitors of ROS production may suppress melanogenesis. Forkhead box-O3a (FoxO3a) is an antimelanogenic factor that mediates ROS-induced skin pigmentation. In this study, we aimed to investigate the whitening effect of mesna and the signaling mechanism mediating this effect. Human melanoma (MNT-1) cells were used in this study. mRNA and protein expression were measured by real-time quantitative PCR and Western blotting analysis to track changes in FoxO3a-related signals induced by mesna. An immunofluorescence assay was performed to determine the nuclear translocation of FoxO3a. When MNT-1 melanoma cells were treated with mesna, melanin production and secretion decreased. These effects were accompanied by increases in FoxO3a activation and nuclear translocation, resulting in downregulation of four master genes of melanogenesis: MITF, TYR, TRP1, and TRP2. We found that mesna, an antioxidant and radical scavenger, suppresses melanin production and may therefore be a useful agent for the clinical treatment of hyperpigmentation disorders.
ABSTRACT
Sodium 2-mercaptoethanesulfonate (mesna) is a protective agent that is widely used in medicine because of its antioxidant effects. Recently, reactive oxygen species (ROS) were shown to increase pigmentation. Thus, ROS scavengers and inhibitors of ROS production may suppress melanogenesis. Forkhead box-O3a (FoxO3a) is an antimelanogenic factor that mediates ROS-induced skin pigmentation. In this study, we aimed to investigate the whitening effect of mesna and the signaling mechanism mediating this effect. Human melanoma (MNT-1) cells were used in this study. mRNA and protein expression were measured by real-time quantitative PCR and Western blotting analysis to track changes in FoxO3a-related signals induced by mesna. An immunofluorescence assay was performed to determine the nuclear translocation of FoxO3a. When MNT-1 melanoma cells were treated with mesna, melanin production and secretion decreased. These effects were accompanied by increases in FoxO3a activation and nuclear translocation, resulting in downregulation of four master genes of melanogenesis: MITF, TYR, TRP1, and TRP2. We found that mesna, an antioxidant and radical scavenger, suppresses melanin production and may therefore be a useful agent for the clinical treatment of hyperpigmentation disorders.
ABSTRACT
BACKGROUND: Over the last decade, the incidence of ultraviolet B (UVB)-related skin problems has increased. Oxidative stress caused by UVB induces the secretion of melanocyte growth and activating factors from keratinocytes, which results in the formation of cutaneous hyperpigmentation. Therefore, increasing the antioxidant abilities of skin cells is thought to be a beneficial strategy for the development of sunscreen agents. Superoxide dismutase 1 (SOD1) is an antioxidant enzyme that is known to exhibit antioxidant properties. OBJECTIVE: The purpose of this study was to investigate the effect of SOD1 on alpha-melanocyte stimulating hormone (alpha-MSH) and UVB-induced melanogenesis in B16F10 melanoma cells and HRM-2 melanin-possessing hairless mice. METHODS: The inhibitory effect of SOD1 on tyrosinase activity was evaluated in a cell-free system. Additional experiments were performed using B16F10 melanoma cells to demonstrate the effects of SOD1 in vitro, and HRM-2 melanin-possessing hairless mice were used to evaluate the antimelanogenic effects of SOD1 in vivo. RESULTS: We found that SOD1 inhibited melanin production in a dose-dependent manner without causing cytotoxicity in B16F10 melanoma cells. SOD1 did not inhibit tyrosinase activity under cell-free conditions. The results indicate that SOD1 may reduce pigmentation by an indirect, nonenzymatic mechanism. We also found that SOD1 decreased UVB-induced melanogenesis in HRM-2 melanin-possessing hairless mice, as visualized through hematoxylin and eosin staining and Fontana-Masson staining. CONCLUSION: Our results indicate that SOD1 has an inhibitory effect on alpha-MSH and UVB-induced melanogenesis, indicating that SOD1 may be a promising sunscreen agent.