Carvone Decreases Melanin Content by Inhibiting Melanoma Cell Proliferation via the Cyclic Adenosine Monophosphate (cAMP) Pathway

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.

The Metabolite Profile in Culture Supernatant of Aster yomena Callus and Its Anti-Photoaging Effect in Skin Cells Exposed to UVB

“…Next, changes in filaggrin, hyaluronic acid synthase 2 (HAS-2), keratin 1 (KRT-1), MMP-3, and MMP-9 expression, which are important factors associated with photoaging [ 35 , 36 , 37 ], were analyzed at the gene level. After examining the mRNA expression of filaggrin, HAS-2, KRT-1, MMP-3, and MMP-9 in UVB-irradiated HaCaT cells treated with AYC-CS-E, we found that the mRNA expressions of filaggrin ( Figure 4 a) and HAS-2 ( Figure 4 b) were higher in UVB-irradiated HaCaT cells treated with AYC-CS-E than those in UVB-irradiated HaCaT cells not treated with AYC-CS-E.…”

Cajanin Suppresses Melanin Synthesis through Modulating MITF in Human Melanin-Producing Cells

“…Interestingly, the expression of MITF also mediates proliferation and differentiation in melanocytes [ 29 ]. It has been reported that natural compound effectively diminished melanin content in melanocytes through suppression of cell proliferation [ 30 ]. The antiproliferative effect and down-regulated MITF-related proteins of cajanin (50 μM) strongly support the further development of this isoflavonoid as an effective anti-melanogenic compound.…”

“…The enzymatic determination of tyrosinase isolated from cajanin-treated human melanin-producing cells was modified from Lv et al, 2020 [ 30 ]. Human MNT1 cells in 6 well-plates (1 × 10 5 cells/well) were cultured in DMEM containing cajanin (0–50 μM) for 24–72 h. Then, the cells were collected by trypsinization and centrifuged at 5000 rpm for 5 min (4 °C).…”

Health Benefits and Pharmacological Properties of Carvone

“…The evaluation of larvicidal activity of Mentha species EOs and their isolated major components against the West Nile virus mosquito (Cx. pipiens 3rd-4th instar larvae) In another experiment [31], carvone was investigated for its ability to reduce melanin content in melanoma cells as well as for its beneficial effects mediated by the cAMP pathway. This study found that carvone decreases the melanin content and inhibits melanoma cell proliferation in a dose-dependent manner.…”