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

We previously demonstrated that alpha-mangostin, gamma-mangostin, and 8-deoxygartanin have significant cytotoxic effects on human melanoma SK-MEL-28 cell line. The current study revealed the underlying mechanisms alpha-Mangostin (7.5 mu g/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 G(1) phase (p21(WAF1) and cyclin D1), apoptosis (cytochrome C, Bcl-2, and Bax), and survival pathways (Akt1, NF kappa B, and I kappa B alpha). alpha-Mangostin significantly upregulated mRNA expression of cytochrome C and p21(WAF1) and downregulated that of cyclin D1, Akt1, and NF kappa B. gamma-Mangostin significantly downregulated mRNA expression of Akt1 and NF kappa B and upregulated p21(WAF1) and I kappa B alpha. 8-Deoxygartanin significantly upregulated the mRNA expression of p21(WAF1) and downregulated that of cyclin D1 and NF kappa B. The three xanthones significantly inhibited the mRNA expression of the BRAF V600E mutation. Moreover, alpha-mangostin and gamma-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.