Significant anti-invasive activities of α-mangostin from the mangosteen pericarp on two human skin cancer cell lines.

AIM: This study aimed at investigating the anti-invasive activities of α-mangostin on human melanoma SK-MEL-28 and squamous cell carcinoma A-431 cell lines. MATERIALS AND METHODS: Cytotoxicity was tested by the crystal violet assay; anti-invasive activity was detected by the wound healing, cell-matrix adhesion, and boyden chamber assays; and gene regulatory effects by qRT-PCR. Treatments were at non-toxic concentrations (0-1.25 µg/ml for A-431 cells and 0-2.5 µg/ml for SK-MEL-28 cells). RESULTS: α-Mangostin inhibited motility, adhesion, migration and invasion. Invasive ability was reduced to 4% and 20% following α-mangostin treatment compared with untreated A-431 and SK-MEL-28 cells, respectively. Inhibition of gene expression of MMP-2, MMP-9, NF-κB, and Akt1 was involved in the anti-invasive activities on A-431 cells. Inhibition of MMP-2, NF-κB and IκBα was involved for SK-MEL-28 cells. CONCLUSION: α-Mangostin suppressed the metastatic processes of SK-MEL-28 and A-431 cell lines by differentially regulating metastasis-related genes, showing potential as an anti-metastatic agent.

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 G(1) phase (93%) significantly increased after 10 µg/ml of MPEE versus untreated SK-MEL-28 cells (78%), which was associated with enhanced p21(WAF1) mRNA levels. In A-431 cells, 10 µg/ml MPEE significantly increased the sub G(1) peak (15%) with concomitant decrease in G(1) 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.

Cytotoxic effect of xanthones from pericarp of the tropical fruit mangosteen (Garcinia mangostana Linn.) on human melanoma cells.

Mangosteen (Garcinia mangostana Linn.) is a tropical tree from South East Asia and its fruit pericarp is a well-known traditional medicine. In this study, the cytotoxic effect of three xanthone compounds (α-mangostin, γ-mangostin, and 8-deoxygartanin) from mangosteen pericarp was investigated using the human melanoma SK-MEL-28 cell line. Significant dose-dependent reduction in % cell viability was induced. γ-Mangostin and 8-deoxygartanine at 5 µg/ml increased the cell cycle arrest in G(1) phase (90% and 92%) compared with untreated cells (78%). All compounds induced apoptosis, of the highest being α-mangostin at 7.5 µg/ml that induced 59.6% early apoptosis, compared to 1.7% in untreated cells. The apoptotic effect of α-mangostin was via caspase activation and disruption of mitochondrial membrane pathways as evidenced by 25-fold increased caspase-3 activity and 9-fold decreased mitochondrial membrane potential when compared to untreated cells. In conclusion, these xanthones, especially α-mangostin, are potential candidates as anti-melanoma agents.