Zeolite 4A, a Synthetic Silicate, Suppresses Melanogenesis through the Degradation of Microphthalmia-Associated Transcription Factor by Extracellular Signal-Regulated Kinase Activation in B16F10 Melanoma Cells

Abstract

In mammals, melanin is the major pigment for the color of human skin and hair. It is synthesized in the melanosomes of melanocytes. This process, called melanogenesis, is a complex phenomenon that occurs in melanocytes by melanogen, cytokine and melanogenic enzymes, such as tyrosinase, tyrosinase-related protein 1 (TRP-1) and tyrosinase-related protein 2 (TRP-2).1) Alpha-melanocyte-stimulating hormone (a-MSH) binds to its specific receptor (MC1R), resulting in activation of GTP-binding protein (Gs), which in turn stimulates adenylate cyclase to produce cAMP.2) The cAMP increases the expression of microphthalmia-associated transcription factor (MITF), which in turn stimulates tyrosinase gene expression.2) Importantly, tyrosinase catalyzes the ratelimiting reaction of the melanogenic process 3) and thus, melanin production is mainly controlled by the expression and activity of tyrosinase. 4)Several known natural melanin synthesis inhibitors, including arbutin and kojic acid, have already been the focus of studies, and are currently being utilized as cosmetic additives.5) However, it is necessary to find safer and more effective skin-whitening agents, because of the carcinogenic potential of kojic acid as well as its weak whitening effect. A great deal of attention has continuously focused on the application of natural products in the cosmetics industry. 6,7)Zeolites have crystalline open framework structures constructed from SiO 4 and AlO 4 tetrahedra linked through oxygen bridges.8-10) Each oxygen atom is shared by two silicon or aluminum atoms. Zeolite is known that silicates and aluminosilicates possess biological activity and also are nontoxic agents. They have been studied in safe oral contrast agent for human magnetic imaging work 11) and in the context of animal feeds.12) Recently, zeolite was found to be a new adjuvant in anticancer therapy, 10) and demonstrated to decreases TiO 2 -photosensitized reactive oxygen species (ROS) generation in cultured human skin fibroblasts. 10,13) In the present study, we demonstrate that zeolite 4A inhibits MITF-mediated tyrosinase expression and melanin synthesis via increasing extracellular signal-regulated kinase (ERK) activity in B16F10 melanoma cells. Cell Cultures B16F10 melanoma cells were generously provided by Dr. Kyoung-Chan Park (Department of Dermatology, Seoul National University), cultured in DMEM (13.4 mg/ml Dulbecco's modified Eagle's medium, 10 mM HEPES, 143 U/ml benzylpenicillin potassium, 100 mg/ml streptomycin sulfate, 24 mM NaHCO 3 , pH 7.1) containing Medicine; Seoul 156-756, Korea: and d Greenjui; 727 Myeomok-Dong, Jungnang-Gu, Seoul 131-835, Korea. Received May 13, 2009; accepted October 2, 2009 Zeolite 4A, synthetic silicate, has been shown to exhibit diverse biological activities such as anti-cancer and anti-oxidant activity. In the present study, we report that the zeolite 4A may improve skin-whitening. We found that zeolite 4A inhibited melanin production in a dose-dependent manner, which has not cytotoxicity. Zeolite 4A also inhibited alp...

Depigmenting Effect of Kojic Acid Esters in Hyperpigmented B16F1 Melanoma Cells

“…It was previously suggested that inhibition of upregulated tyrosinase enzyme in melanoma cells might inhibit cell proliferation of melanoma cells [42, 43]. This is due to the correlation of microphthalmia-associated transcription factor (MITF) and extracellular signal-regulated kinase (ERK) in the pigmentation, proliferation, and survival of melanocytes and melanoma [23, 26, 35]. Due to this reason, it was expected that the inhibition of MITF expression may also inhibit melanoma cells proliferation.…”

“…Cellular tyrosinase activity was determined according to the method described by Shin et al [23]. In this method, B16F1 melanoma cells were treated with α -MSH alone and α -MSH with the addition of KA and KA esters at various doses for a total of 72 h incubation.…”

In vitro and in vivo studies disclosed the depigmenting effects of gallic acid: A novel skin lightening agent for hyperpigmentary skin diseases

“…Pigmentation is one of the most common skin conditions affecting people of all colors and all ages worldwide. In mammals, melanin is the major pigment for the color of human skin and hair, and it is synthesized in the melanosomes of melanocytes [1]. The synthesis of both eumelanin and pheomelanin require melanocyte‐specific enzymes, including tyrosinase, TRP‐1, and Dct.…”

Inhibitory Effects of (2′R)‐2′,3′‐dihydro‐2′‐(1‐hydroxy‐1‐methylethyl)‐2,6′‐bibenzofuran‐6,4′‐diol on Mushroom Tyrosinase and Melanogenesis in B16‐F10 Melanoma Cells

“…Tyrosinase activity analysis by zymography. Tyrosinase activity was determined by zymography, as previously described (Shin et al, 2010). After being co-treated with DHMB and IBMX for 72 h, the cells were lysed in PBS (pH 6.8) containing 1% Triton X-100, 1 mM phenylmethanesulfonylfluoride and protease inhibitor cocktail (Sigma, St. Louis, MO, USA).…”