Anti-skin cancer properties of phenolic-rich extract from the pericarp of mangosteen (Garcinia mangostana Linn.)

Skin cancers are often resistant to conventional chemotherapy. This study examined the anti-skin cancer properties of crude ethanol extract of mangosteen pericarp (MPEE) on human squamous cell carcinoma A-431 and melanoma SK-MEL-28 lines. Significant dose-dependent reduction in% viability was observed for these cell lines, with less effect on human normal skin fibroblast CCD-1064Sk and keratinocyte HaCaT cell lines. Cell distribution in G1 phase (93%) significantly increased after 10 μg/ml of MPEE versus untreated SK-MEL-28 cells (78%), which was associated with enhanced p21WAF1 mRNA levels. In A-431 cells, 10 μg/ml MPEE significantly increased the sub G1 peak (15%) with concomitant decrease in G1 phase over untreated cells (2%). In A-431 cells, 10 μg/ml MPEE induced an 18% increase in early apoptosis versus untreated cells (2%). This was via caspase activation (15-, 3- and 4-fold increased caspse-3/7, 8, and 9 activities), and disruption of mitochondrial pathways (6-fold decreased mitochondrial membrane potential versus untreated cells). Real-time PCR revealed increased Bax/Bcl-2 ratio and cytochrome c release, and decreased Akt1. Apoptosis was significantly increased after MPEE treatment of SK-MEL-28 cells. Hence, MPEE showed strong anti-skin cancer effect on these two skin cancer cell lines, with potential as an anti-skin cancer agent.

► Mangosteen pericarp ethanol extract possesses a high level of antioxidants. ► Mangosteen pericarp ethanol extract exhibits significant and selective cytotoxicity on two skin cancer cell lines. ► Cell cycle arrest in G1 phase associated with upregulating mRNA level of p21WAF1 was observed. ► Apoptosis was induced via intrinsic and/or extrinsic pathway with caspase activation and mitochondrial membrane disruption. ► Altered mRNA expression of Bcl-2, Bax, cytochrome c, Akt1 was observed.