The inhibitory effect of glycolic acid and lactic acid on melanin synthesis in melanoma cells

Abstract

Alpha-hydroxy acids (AHAs) such as glycolic acid (GA) and lactic acid (LA) have been reported to be effective in treating pigmentary lesions such as melasma, solar lentigines, and postinflammatory hyperpigmentation. The mechanism of this effect might be due to epidermal remodeling and accelerated desquamation, which would result in quick pigment dispersion. However, the direct effect of AHAs on melanin synthesis has not yet been well studied. To elucidate such a direct effect of AHAs on melanogenesis, we performed melanin assays, growth curve determinations, Northern and Western blotting for melanogenic proteins [tyrosinase, tyrosinase related protein (TRP)-1 and TRP-2], and tyrosinase and, 4-dihydroxyphenylalaninechrome tautomerase enzyme activity assays using mouse B16 and human melanoma cells. GA or LA (at doses of 300 or 500 microg/ml) inhibited melanin formation in similar dose-dependent manner, without affecting cell growth. Although the mRNA and protein expression or molecular size of tyrosinase, TRP-1 and TRP-2 were not affected, tyrosinase activity was inhibited. To see whether GA and/or LA directly inhibit tyrosinase catalytic function, the effect of GA and LA on human tyrosinase purified from the melanosome-rich large granule fraction of human melanoma cells was performed. GA or LA were shown to inhibit tyrosinase enzyme activity directly, but this effect was not due to the acidity of GA or LA, because adjusting the pH to 5.6 (the pH of GA and LA at concentrations of 2500 microg/ml), did not affect tyrosinase activity. Taken together, these results show that GA and LA suppress melanin formation by directly inhibiting tyrosinase activity, an effect independent of their acidic nature. GA and LA might work on pigmentary lesions not only by accelerating the turnover of the epidermis but also by directly inhibiting melanin formation in melanocytes.

Treatment of Periorbital dark circles: Comparative study of chemical peeling with a combination of trichloroacetic acid and lactic acid versus carboxytherapy

“…Lactic acid is an alpha hydroxy acid (AHA) which facilitates desquamation of epidermal cells, melanin dispersion, and induces collagen and glycosaminoglycan deposition. Moreover, it has been reported to inhibit tyrosinase enzyme; therefore it was used in the treatment of melasma [20] . It induces the skin-lightening effect through three mechanisms, namely the induction of keratinocytes desquamation and the removal of melanosomes; the inhibition of tyrosinase; and the thickening of the epidermis and the dermis, so that the vasculatures become less visible [21,22] .…”

The melanogenesis and mechanisms of skin‐lightening agents – existing and new approaches

“…Tyrosinase activity was inhibited. No effect on tyrosinase, TRP-1 and TRP-2 mRNA [98] Study on topical application of a 10% glycolic acid for melasma showed improvement in 91% of patients [138].…”

“…Except for their activity on acceleration of epidermal turnover [59,60,65,[95][96][97], several of these acids have also been shown to have effect on tyrosinase. For example, a-hydroxyacids is complementing its action on desquamation with direct inhibition of tyrosinase without influencing mRNA or protein expression [65,97,98]. The smallest a-hydroxy acid is glycolic acid (hydroxyacetic acid or 2-hydroxyethanoic acid).…”

Chemical peeling in ethnic skin: an update

“…35 Work by Sachdeva 36 has shown that lactic acid may be used for the treatment of acne scarring with minimal risk of any adverse events. In addition, Sharquie et al…”