Antitumor activity of curcumin is involved in down-regulation of YAP/TAZ expression in pancreatic cancer cells

Abstract

// Xiuxia Zhou 1, * , Jingna Su 1, * , Shaoyan Feng 2, * , Lixia Wang 1 , Xuyuan Yin 1 , Jingzhe Yan 3 , Zhiwei Wang 1, 4 1 The Cyrus Tang Hematology Center and Collaborative Innovation Center of Hematology, Jiangsu Institute of Hematology, The First Affiliated Hospital, Soochow University, Suzhou 215123, China 2 Department of Otolaryngology, The fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, 519020, China 3 Department of Abdominal Oncosurgery, Jilin province Cancer Hospital, Changchun, Jilin, 130012, China 4 Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA * These authors have contributed equally to this work Correspondence to: Jingzhe Yan, email: yanjzhe@163.com Zhiwei Wang, email: zwang6@bidmc.harvard.edu Keywords: curcumin, pancreatic cancer, Skp2, invasion, proliferation Received: September 02, 2016     Accepted: September 26, 2016     Published: October 12, 2016 ABSTRACT Pancreatic cancer (PC) is one of the most aggressive human malignancies worldwide and is the fourth leading cause of cancer-related deaths. Curcumin (diferuloylmethane) is a polyphenol derived from the Curcuma longa plant. Certain studies have demonstrated that curcumin exerts its anti-tumor function in a variety of human cancers including PC, via targeting multiple therapeutically important cancer signaling pathways. However, the detailed molecular mechanisms are not fully understood. Two transcriptional co-activators, YAP (Yes-associated protein) and its close paralog TAZ (transcriptional coactivator with PDZ-binding motif) exert oncogenic activities in various cancers. Therefore, in this study we aimed to determine the molecular basis of curcumin-induced cell proliferation inhibition in PC cells. First, we detected the anti-tumor effects of curcumin on PC cell lines using CTG assay, Flow cytometry, clonogenic assay, wound healing assay and Transwell invasion assay. We found that curcumin significantly suppressed cell growth, weakened clonogenic potential, inhibited migration and invasion, and induced apoptosis and cell cycle arrest in PC cells. We further measured that overexpression of YAP enhanced cell proliferation and abrogated the cytotoxic effects of curcumin on PC cells. Moreover, we found that curcumin markedly down-regulated YAP and TAZ expression and subsequently suppressed Notch-1 expression. Collectively, these findings suggest that pharmacological inhibition of YAP and TAZ activity may be a promising anticancer strategy for the treatment of PC patients.