Nifuratel, a novel STAT3 inhibitor with potent activity against human gastric cancer cells

Abstract

Hailun Zheng,1,2,* Huang Hong,1,* Lulu Zhang,1,2,* Xiong Cai,1,2 Meng Hu,1,2 Yuepiao Cai,2 Bin Zhou,1 Jiayuh Lin,3 Chengguang Zhao,2 Wanle Hu1 1Department of Coloproctology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, 2Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 3Department of Biochemistry and Molecular Biology, University of Maryland Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MA, USA *These authors contributed equally to this work Abstract: Activation of the signal transducer and activator of transcription 3 (STAT3) is observed in multiple cancer types, including gastric cancer, and represents a potential drug target for chemotherapy. Currently, clinically available small-molecule inhibitors targeting STAT3 are lacking. Here, we report that nifuratel, an antiprotozoal and antifungal drug, is a potent inhibitor of STAT3. We found that nifuratel significantly suppressed proliferation and induced apoptosis of gastric cancer cells. Studies of the mechanism of action of nifuratel indicated that it acts by inhibiting the constitutive and interleukin-6-induced STAT3 activation. Taken together, our findings demonstrate that nifuratel may be a novel, clinically accessible STAT3 inhibitor in gastric cancer cells. Keywords: nifuratel, STAT3, gastric cancer, inhibitor, drug

Keywords

• Nifuratel
• STAT3
• Gastric cancer
• Inhibitor
• Drug