Abstract
Melanin, which determines the color of the skin and hair, is initially synthesized to protect the skin from ultraviolet light; however, excessive melanin pigmentation caused by abnormal cell proliferation can result in various melanocytic lesions. Cyclic adenosine monophosphate (cAMP) is known to regulate cell cycle progression and consequently to inhibit the division of abnormally proliferating cells. In this work, we aimed to test whether carvone, a scent compound from plants, inhibits proliferation and subsequently reduces melanin content of melanoma cells and to determine whether its beneficial effects are mediated by the cAMP pathway. We found that carvone decreases melanin content and inhibits melanoma cell proliferation in a concentration-dependent manner. Meanwhile, it inhibited the activation of cell cycle-associated proteins such as cyclin-dependent kinase 1 (CDK1). Of note, the beneficial effects of carvone were abrogated by cAMP inhibition. Our findings indicate potential benefits of carvone for the treatment of melanomas and presumably other hyperpigmentation-related dermatological disorders such as melasmas, lentigines, and excessive freckles.
Highlights
Melanin, the end product of melanogenesis, is produced exclusively in melanocytes and determines the color of human skin, eyes, and hair
To investigate the effect of carvone on cell death, the B16F10 melanoma cells were treated withwith either vehicle (dimethyl sulfoxide (DMSO))
We demonstrated that the the phosphorylation of cell division cycle 25B (Cdc25B) and cyclin-dependent kinase 1 (CDK1)
Summary
The end product of melanogenesis, is produced exclusively in melanocytes and determines the color of human skin, eyes, and hair. The major contributing factor of these melanocytic lesions is the loss of control of cell proliferation owing to ultraviolet-induced damage and other environmental factors, such as stress [3,4,5,6,7]. It is well known that cAMP regulates cell cycle progression: In many tumor cells with high proliferation rates, cAMP is a negative regulator (secondary messenger) of proliferation, with lower basal cAMP levels in most tumor cells than those in normal cells [10,11,12,13]. In melanoma cells, the elevation of cAMP concentrations by treatment with forskolin (an adenylyl cyclase (ADCY) activator) delays cell cycle progression and cell proliferation [14]. Other cAMP-upregulating agents such as 8-bromo-cAMP (a cAMP analog) and erythro-9-(2-hydroxy-3-nonyl) adenine (a cAMP phosphodiesterase 2 inhibitor) have been shown to inhibit melanoma cell growth [15]
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