Plumbagin Suppresses α-MSH-Induced Melanogenesis in B16F10 Mouse Melanoma Cells by Inhibiting Tyrosinase Activity

Abstract

Recent studies have shown that plumbagin has anti-inflammatory, anti-allergic, antibacterial, and anti-cancer activities; however, it has not yet been shown whether plumbagin suppresses alpha-melanocyte stimulating hormone (α-MSH)-induced melanin synthesis to prevent hyperpigmentation. In this study, we demonstrated that plumbagin significantly suppresses α-MSH-stimulated melanin synthesis in B16F10 mouse melanoma cells. To understand the inhibitory mechanism of plumbagin on melanin synthesis, we performed cellular or cell-free tyrosinase activity assays and analyzed melanogenesis-related gene expression. We demonstrated that plumbagin directly suppresses tyrosinase activity independent of the transcriptional machinery associated with melanogenesis, which includes micropthalmia-associated transcription factor (MITF), tyrosinase (TYR), and tyrosinase-related protein 1 (TYRP1). We also investigated whether plumbagin was toxic to normal human keratinocytes (HaCaT) and lens epithelial cells (B3) that may be injured by using skin-care cosmetics. Surprisingly, lower plumbagin concentrations (0.5–1 μM) effectively inhibited melanin synthesis and tyrosinase activity but do not cause toxicity in keratinocytes, lens epithelial cells, and B16F10 mouse melanoma cells, suggesting that plumbagin is safe for dermal application. Taken together, these results suggest that the inhibitory effect of plumbagin to pigmentation may make it an acceptable and safe component for use in skin-care cosmetic formulations used for skin whitening.

Natural and Bioinspired Phenolic Compounds as Tyrosinase Inhibitors for the Treatment of Skin Hyperpigmentation: Recent Advances

“…At present, though a wide range of tyrosinase inhibitors from natural and synthetic sources have been reported, only a few of them, in addition to being effective, are known as safe compounds. No significant advances concerning toxicity issues of tyrosinase inhibitors seem to emerge from the literature survey carried out for this review, the relevant papers just reporting the results of in vitro cytotoxicity experiments [49,52,75,81,95,126,129,[131][132][133]136,137,147,163,[176][177][178]184,185,192,198,202,203,207,210,212,214,215,239,240,242,245] and only a few of in vivo experiments on zebrafish [130,206,209]. Therefore, it is essential to examine the efficacy and safety of inhibitors by checking e.g., whether or not the candidate inhibitor is substrate of tyrosinase being modified on exposure to the enzyme.…”

Beauvericin inhibits melanogenesis by regulating cAMP/PKA/CREB and LXR-α/p38 MAPK–mediated pathways

“…Cyclic AMP leads to activation of PKA, followed by phosphorylation of CREB transcription factor. CREB stimulates expression of the MITF gene, leading to an increase of melanin levels 35 . In this study, beauvericin reduced cAMP levels and suppressed CREB phosphorylation as well as PKA activity.…”

Antimelanogenic Effects of Polygonum tinctorium Flower Extract from Traditional Jeju Fermentation via Upregulation of Extracellular Signal-Regulated Kinase and Protein Kinase B Activation

“…Although it is different from normal human melanocyte and human melanoma cell lines in various cellular behaviors [ 26 , 27 , 28 ], this cell line is also an excellent model for studying the effects of extracts/compounds on melanin production [ 29 ]. Numerous studies have found that upregulation of melanogenesis is often observed in malignant melanoma with overexpressed tyrosinase levels in blood as well as tumor tissues [ 30 ]. In addition, MITF has been reported as an amplified oncogene in human melanomas and displays functional roles in transcriptional gene expression related to survival, proliferation, cell cycle progression and chemoresistance [ 31 ].…”