Altered mRNA Expression Related to the Apoptotic Effect of Three Xanthones on Human Melanoma SK-MEL-28 Cell Line

Abstract

We previously demonstrated thatα-mangostin,γ-mangostin, and 8-deoxygartanin have significant cytotoxic effects on human melanoma SK-MEL-28 cell line. The current study revealed the underlying mechanisms.α-Mangostin (7.5 μg/mL) activated caspase activity, with a 3-fold and 4-fold increased caspase 8 and 9 activity, respectively. The molecular mechanisms were investigated by qRT-PCR for mRNA related to cell cycle arrest in G1phase (p21WAF1and cyclin D1), apoptosis (cytochrome C, Bcl-2, and Bax), and survival pathways (Akt1, NFκB, and IκBα).α-Mangostin significantly upregulated mRNA expression of cytochrome C andp21WAF1and downregulated that of cyclin D1, Akt1, and NFκB.γ-Mangostin significantly downregulated mRNA expression of Akt1 and NFκB and upregulatedp21WAF1and IκBα. 8-Deoxygartanin significantly upregulated the mRNA expression ofp21WAF1and downregulated that of cyclin D1 and NFκB. The three xanthones significantly inhibited the mRNA expression of the BRAF V600E mutation. Moreover,α-mangostin andγ-mangostin significantly downregulated Akt phosphorylation at Ser473. In conclusion, the three xanthones induced an inhibitory effect on SK-MEL-28 cells by modulating the molecular targets involved in the apoptotic pathways.