7,8-Dihydroxyflavone induces mitochondrial apoptosis and down-regulates the expression of ganglioside GD3 in malignant melanoma cells

Abstract

Malignant melanoma is one of the most progressive skin cancers, with a poor prognosis, various side effects, and high resistance to conventional treatment. Recently, 7,8-dihydroxyflavone (7,8-DHF), a polyphenolic flavonoid derived from certain plants, has been studied for its anti-carcinogenic, anti-inflammatory, antioxidant, and pharmacological effects in several types of cancer. Ganglioside, a modulator of diverse cell signals on the microdomain of the surface of the cell membrane, is closely involved in various cancers such as neuroblastoma. However, the correlation between ganglioside expression and the anti-cancer effects of 7,8-DHF in malignant melanoma remains unclear. In this study, 7,8-DHF showed potential as an anti-cancer agent through specific anti-proliferation, anti-oxidant, anti-migration, pro-apoptotic, and G2/M phase cell cycle arrest effects on SK-MEL-2 and G-361 melanoma cells. In contrast, 7,8-DHF did not induce cytotoxicity in non-tumoral epidermal HaCaT cells. Additionally, we confirmed for the first time that 7,8-DHF significantly reduces the expression levels of ganglioside GD3, which is closely involved in carcinogenesis, in both melanoma cancer cell lines using high-performance thin-layer chromatography analysis. Taken together, our findings suggest that 7,8-DHF might be a potent anticancer drug candidate for the treatment of malignant melanoma.