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

Abstract

Malignant melanoma is a skin cancer with poor prognosis and high resistance to conventional treatment. 7,8-dihydroxyflavone (7,8-DHF) has shown anti-carcinogenic, anti-inflammatory, anti-oxidant, and pharmacological effects in several types of cancer. However, the relationship between ganglioside expression and the anti-cancer effects of 7,8-DHF in melanoma is not fully understood. In the present study, 7,8-DHF exhibits specific anti-proliferation, anti-migration, and G2/M phase cell-cycle arrest effects on both melanoma cancer cell lines, and induces mitochondrial dysfunction and apoptosis, making it a potent candidate for anti-melanoma treatment. Furthermore, we confirmed that 7,8-DHF significantly reduces the expression levels of ganglioside GD3 and its synthase, which are known to be closely involved in carcinogenesis. Taken together, our findings suggest that 7,8-DHF may be a potent anti-cancer drug candidate for the treatment of malignant melanoma.

Quercetin Induces Mitochondrial Apoptosis and Downregulates Ganglioside GD3 Expression in Melanoma Cells

“…The examination of ganglioside expression in melanoma cells revealed elevated levels of both ganglioside GD3 and GM3, consistent with prior reports [47,48]. Quercetin treatment effectively decreased the expression levels of these gangliosides, aligning with findings using other flavonoid drugs [49]. The data suggest ganglioside GM3 and GD3 as potential specific markers for melanoma cells, potentially serving as therapeutic targets in these cancers.…”

Using Flavonoid Substitution Status to Predict Anticancer Effects in Human Melanoma Cancers: An In Vitro Study

“…On the other hand, 15 activated the intrinsic apoptosis pathway by the induction of caspase-9 in C32 cells. A previous investigation indicated that 16 is an activator of caspase-3 and c-PARP in SK-MEL-2 and G-361 melanoma cells [27]. Consistent with these findings, 16 induced apoptosis in both A375 and C32 cell lines.…”

“…In contrast to 15, flavonoid 16 has already been reported as an anticancer agent in two human malignant melanoma cell lines (SK-MEL-2 and G-361). In the MTS test, the inhibition of the viability by 7,8dihydroxyflavone (16) was significant in both melanoma cell lines (IC 50 values were in the range of 200-250 µM) [27]. Moreover, 17, selected in our survey as the most active in the cell viability test, is mentioned in only a few studies for its anticancer activity (e.g., HeLa, SCC, MCF-7, U251N, and PANC-1 cell lines) [21,[28][29][30].…”

“…Extensive biological in vitro studies led to identifying which flavonoid substitution patterns play a crucial role in their anticancer activity, which allowed for the demonstration of the structureactivity relationships (SARs). Thus, in this study, we investigated the anti-cancer potential of 37 flavonoids to identify active compounds: apigenin (1), apigenin 8-C-glucoside (vitexin) (2), apigenin 7-O-glucoside (3), apigenin 7-O-glucuronide (4), apigenin 7-Orutinoside (5), luteolin (6), luteolin 7-O-glucoside (cynaroside) (7), luteolin 7-O-glucuronide (8), luteolin 7-O-sambubioside (9), 5,7,3 ′ -trihydroxy-4 ′ -acetoxy-flavone-8-C-xyloside-2 ′′ -O-glucoside (scleranthoside A) (10), 5,7,3 ′ -trihydroxy-4 ′ -methoxyflavone-8-C-xyloside-2 ′′ -O-glucoside (scleranthoside B) (11), 5,7-dihydroxy-3 ′ -methoxy-4 ′ -acetoxyflavone-8-Cxyloside-2 ′′ -O-(4 ′′′ -acetoxy)-glucoside (scleranthoside C) (12), 5,7-dihydroxy-3 ′ -methoxy-4 ′ -acetoxyflavone-8-C-arabinoside-2 ′′ -O-(4 ′′′ -acetoxy)-glucoside (scleranthoside D) (13), chrysin (14), 5,6-dihydroxyflavone (15), 7,8-dihydroxyflavone (16), zapotin (17), kaempferol (18), 8-methoxykaempferol (19), kaempferol 3-O-glucoside (astragalin) (20), kaempferol 3-Oglucuronide (21), kaempferol 3-O-galactoside (hyperoside) (22), icariin (23), quercetin (24), 7-methoxyquercetin (rhamnetin) (25), 3 ′ -methoxyquercetin (isorhamnetin) (26), quercetin 3-O-glucuronide (27), quercetin 3-O-rutinoside (rutin) (28), quercetin 3-O-rutinoside-7-O-glucoside (29), myricetin (30), tricin (31), robinetin (32), hesperetin (33), hesperetin 7-O-rutinoside (hesperidin) (34), hesperetin 7-O-neohesperidoside (neohesperidin) (35), daidzein (36), and genistein (37). The chemical and biological properties of flavonoids and their der...…”