OSU-A9 inhibits pancreatic cancer cell lines by modulating p38-JAK-STAT3 signaling

// Wan-Chi Tsai 1, 2 , Li-Yuan Bai 3, 4 , Yi-Jin Chen 1 , Po-Chen Chu 5, 6 , Ya-Wen Hsu 7 , Aaron M. Sargeant 8 , Jing-Ru Weng 9 1 Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan 2 Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung 80708, Taiwan 3 College of Medicine, China Medical University, Taichung 40402, Taiwan 4 Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital, Taichung 40447, Taiwan 5 Institute of Biological Chemistry, Academia Sinica, Taipei 11574, Taiwan 6 Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan 7 Department of Hospital and Health Care Administration, Chia Nan University of Pharmacy & Science, Tainan 71745, Taiwan 8 Charles River Laboratories, Safety Assessment, Spencerville, OH 45887, USA 9 Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung 80424, Taiwan Correspondence to: Jing-Ru Weng, email: columnster@gmail.com Keywords: OSU-A9, pancreatic cancer, p38, JAK, STAT3 Received: January 05, 2016      Accepted: February 27, 2017      Published: March 22, 2017 ABSTRACT Pancreatic cancer is an aggressive malignancy that is the fourth leading cause of death worldwide. Since there is a dire need for novel and effective therapies to improve the poor survival rates of advanced pancreatic cancer patients, we analyzed the antitumor effects of OSU-A9, an indole-3-carbinol derivative, on pancreatic cancer cell lines in vitro and in vivo . OSU-A9 exhibited a stronger antitumor effect than gemcitabine on two pancreatic cancer cell lines, including gemcitabine-resistant PANC-1 cells. OSU-A9 treatment induced apoptosis, the down-regulation of Akt phosphorylation, up-regulation of p38 phosphorylation and decreased phosphorylation of JAK and STAT3. Cell migration and invasiveness assays showed that OSU-A9 reduced cancer cell aggressiveness and inhibited BxPC-3 xenograft growth in nude mice. These results suggest that OSU-A9 modulates the p38-JAK-STAT3 signaling module, thereby inducing cytotoxicity in pancreatic cancer cells. Continued evaluation of OSU-A9 as a potential therapeutic agent for pancreatic cancer thus appears warrented.