α-Mangostin suppresses the viability and epithelial-mesenchymal transition of pancreatic cancer cells by downregulating the PI3K/Akt pathway.

Qinhong Xu,Xuqi Li,Erxi Wu,Ang Hu,Wanxing Duan,Jianjun Lei,Jiguang Ma,Qingyong Ma,Zheng Wu,Xin Chen,Liang Sheng,Zheng Wang

doi:10.1155/2014/546353

Abstract

α-Mangostin, a natural product isolated from the pericarp of the mangosteen fruit, has been shown to inhibit the growth of tumor cells in various types of cancers. However, the underlying molecular mechanisms are largely unclear. Here, we report that α-mangostin suppressed the viability and epithelial-mesenchymal transition (EMT) of pancreatic cancer cells through inhibition of the PI3K/Akt pathway. Treatment of pancreatic cancer BxPc-3 and Panc-1 cells with α-mangostin resulted in loss of cell viability, accompanied by enhanced cell apoptosis, cell cycle arrest at G1 phase, and decrease of cyclin-D1. Moreover, Transwell and Matrigel invasion assays showed that α-mangostin significantly reduced the migration and invasion of pancreatic cancer cells. Consistent with these results, α-mangostin decreased the expression of MMP-2, MMP-9, N-cadherin, and vimentin and increased the expression of E-cadherin. Furthermore, we found that α-mangostin suppressed the activity of the PI3K/Akt pathway in pancreatic cancer cells as demonstrated by the reduction of the Akt phosphorylation by α-mangostin. Finally, α-mangostin significantly inhibited the growth of BxPc-3 tumor mouse xenografts. Our results suggest that α-mangostin may be potentially used as a novel adjuvant therapy or complementary alternative medicine for the management of pancreatic cancers.

Highlights

Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant and lethal tumors, with an overall 5-year survival rate less than 5% [1]
Antibodies against Bcl2 or β-actin were from Santa Cruz Biotechnology (Santa Cruz, CA, USA); anticleaved caspase-3, cyclin-D3, cyclin-D1, Akt, and phospho-Akt (Ser473) antibodies were purchased from Cell Signaling Technology; anti-MMP-2 and antiMMP-9 antibodies were from Proteintech (USA); antibodies against E-cadherin, N-cadherin, and vimentin were procured from Bioworld (Minneapolis, MN, USA)
When compared to the untreated group, more than 30% cells of both of the cell lines underwent apoptosis following treatment of 16 μM α-mangostin (Figures 2(a) and 2(b), P < 0.05). Consistent with these results, immunoblots demonstrated that α-mangostin caused a dosedependent reduction in the antiapoptosis Bcl-2 protein levels and an increase in the levels of cleaved of caspase-3, a marker of cell apoptosis (Figure 2(c)). These results clearly demonstrate that α-mangostin induces apoptosis of pancreatic cancer cells

Summary

Introduction

Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant and lethal tumors, with an overall 5-year survival rate less than 5% [1]. The pericarp of this fruit has been used as a native drug by Southeast Asians to treat diseases, such as skin infections and wounds, amoebic dysentery, diarrhoea, and BioMed Research International cholera [6]. Commercial products comprised of mangosteen, multiple vitamins and minerals, green tea, and other natural extracts are being widely recommended to cancer patients as a dietary supplement [7]. There is no sufficient clinical evidence that mangosteen could suppress the growth of tumors or reduce the incidence of malignancies, the commercial products are one of the bestselling botanical dietary supplements [8]

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Results

Conclusion