α-Mangostin Suppresses the Viability and Epithelial-Mesenchymal Transition of Pancreatic Cancer Cells by Downregulating the PI3K/Akt Pathway

نویسندگان

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

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.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Long non-coding RNA FOXO1 inhibits lung cancer cell growth through down-regulating PI3K/AKT signaling pathway

Objective(s): Lung cancer is one of the most common malignant tumors, which seriously threatens the health and life of the people. Recently, a novel long non-coding RNA (lncRNA) termed lncFOXO1 was found and investigated in breast cancer. However, the effect of lncFOXO1 on lung cancer is still ambiguous. The current study aimed to uncover the functions of lncFOXO1 in l...

متن کامل

Epithelial to mesenchymal transition concept in Cancer: Review article

Owing to this fact that most of the mortalities in cancers are as a result of metastasis, study on the involved pathways in metastasis including Epithelial to mesenchymal transition (EMT) would be so critical and important. Up to date, several extensive studies have been carried out to determine the correlation between EMT and cancer and their results have shown that the EMT plays pivotal role ...

متن کامل

HS-173, a novel PI3K inhibitor suppresses EMT and metastasis in pancreatic cancer

Pancreatic cancer is one of the most aggressive solid malignancies prone to metastasis. Epithelial-mesenchymal transition (EMT) contributes to cancer invasiveness and drug resistance. In this study, we investigated whether HS-173, a novel PI3K inhibitor blocked the process of EMT in pancreatic cancer. HS-173 inhibited the growth of pancreatic cancer cells in a dose- and time-dependent manner. M...

متن کامل

Knockdown of PFTK1 inhibits tumor cell proliferation, invasion and epithelial-to-mesenchymal transition in pancreatic cancer.

PFTK1 was identified as a member of the cyclin-dependent kinase (CDK) family and it is frequently upregulated in many types of tumors. However, its expression and role in pancreatic cancer has not been yet reported. In this study, we aimed to explore the expression and function in pancreatic cancer. The present study verified that PFTK1 was highly expressed in pancreatic cancer cell lines. The ...

متن کامل

Salvianolic acid B improves insulin secretion from interleukin 1β-treated rat pancreatic islets: The role of PI3K-Akt signaling

Background and Objective: Oxidative stress induced by proinflammatory cytokines such as IL-1β plays a major role in β-cell destruction in diabetes type 1. Salvianolic acid B (Sal B) is a polyphenolic compound with antioxidant and protective effects. Thus, objective of this study was to assess the protection exerted by Sal B on isolated rat islets exposed to IL-1β and to investigate an underlyin...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:

دوره 2014  شماره 

صفحات  -

تاریخ انتشار 2014