Differential sensitivities of bladder cancer cell lines to resveratol are unrelated to its metabolic profile

Abstract

// Yang Yang 1, 2, * , Chuangang Li 3, * , Hong Li 4 , Moli Wu 4 , Changle Ren 5 , Yuhong Zhen 1 , Xiaochi Ma 1 , Yunpeng Diao 1 , Xiaodong Ma 1 , Sa Deng 1 , Jia Liu 4 and Xiaohong Shu 1, 2, * 1 College of Pharmacy, Dalian Medical University, Dalian, Liaoning, China 2 Academy of Integrative Medicine, Dalian Medical University, Dalian, Liaoning, China 3 Surgery Department of The Second Affiliated Hospital, Dalian Medical University, Dalian, Liaoning, China 4 College of Basic Medical Sciences, Dalian Medical University, Dalian, Liaoning, China 5 Surgery Department of Dalian Municipal Central Hospital, Dalian Medical University, Dalian, Liaoning, China * These authors have contributed equally to this work Correspondence to: Xiaohong Shu, email: xiaohong_shu@dmu.edu.cn Keywords: bladder cancer, resveratrol, metabolism, chemosensitivity, sulfotransferase 1A1 Received: October 11, 2016     Accepted: January 09, 2017     Published: February 02, 2017 ABSTRACT Resveratrol (RV) is a natural polyphenol compound with a wide range of activities, including inhibition of human bladder cancer (HBC) cell growth. Because RV is rapidly metabolized and has poor bioavailability, it is unclear whether the antitumor activity is due to RV or its metabolites. We therefore used liquid chromatography-mass spectroscopy, qRT-PCR, immunocytochemistry and western blotting to evaluate the metabolic profile and biotransformation of RV in the T24 and EJ HBC cell lines. Both T24 and EJ cells generated the same RV metabolite, RV monosulfate (RVS), and both exhibited upregulation of the RV-associated metabolic enzyme SULT1A1 (sulfotransferase). Despite these similarities, T24 cells were more sensitive to RV than EJ cells, yet T24 cells exhibited no sensitivity to an RVS mixture (84.13% RVS). Primary rat bladder epithelial cells showed no adverse effects when exposed to a therapeutic dose (100 μM) of RV. The differences in RV sensitivity between the two HBC cell lines did not reflect differences in the RV metabolic profile or SULT1A1 expression. Because RV exhibited stronger antitumor activity and better safety than RVS, we conclude that RV has significant therapeutic potential for HBC treatment, provided individual differences are considered during clinical research and application.