Objectives: Phragmenthera capitata (Spreng.) Balle and Globimetula braunii (Engler.) Van Tiegh are African mistletoe traditionally used in cancers treatment. Thus, the aim of the study was to assess the anti-melanoma potential of the methanol extract of Phragmenthera capitata (Spreng.) Balle (PCMe-OH) and Globimetula braunii (Engler.) (GBMe-OH) Van Tiegh.
Methods: Antioxidant potential was evaluated using DPPH, FRAP and hydroxyl assays. Total flavonoid and phenolic contents was also determined. MTT assay was used to estimate the effects on cell viability using SK-MLE28 and B16-F10 cell lines. Colony formation and wound healing were also assessed. Fluorometry methods were used for qualitative analysis of apoptosis and estimate ROS production. Western blot analysis was used for protein expression.
Results: Phragmenthera capitata (PCMe-OH) showed the highest antioxidant activity and possess the highest phenolic contents (1,490.80 ± 55 mgGAE/g extract) in comparison with G. braunii (GBMe-OH) and (1,071.40 ± 45 mgGAE/g extract). Flavonoid content was similar in both extracts (11.63 ± 5.51 mg CATE/g of extract and 12.46 ± 2.58 mg CATE/g of extract respectively). PC-MeOH showed the highest cytotoxicity effect (IC50 of 55.35 ± 1.17 μg/mL) and exhibited anti-migrative potential on B16-F10 cells. Furthermore, PC-MeOH at 55.35 and 110.7 μg/mL; promoted apoptosis-induced cell death in B16-F10 cells by increasing intracellular ROS levels and reducing Bcl-2 expression level at 110.7 μg/mL. Significant upregulation of P-PTEN expression was recorded with PC-MeOH at 110.7 μg/mL; inhibiting therefore PI3K/AKT/m-Tor signaling pathway. Moreover, at 55.37 μg/mL significant reduction of c-myc and cyclin D1 was observed; dysregulating the MAPK kinase signaling pathway and cell cycle progression.
Conclusions: Phragmenthera capitata may be developed into selective chemotherapy to fight against melanoma.
Keywords: Phragmenthera capitata; MAPK kinase; anti-melanoma; apoptosis.
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