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

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.
AuthorsYang Yang, Chuangang Li, Hong Li, Moli Wu, Changle Ren, Yuhong Zhen, Xiaochi Ma, Yunpeng Diao, Xiaodong Ma, Sa Deng, Jia Liu, Xiaohong Shu
JournalOncotarget (Oncotarget) Vol. 8 Issue 25 Pg. 40289-40304 (Jun 20 2017) ISSN: 1949-2553 [Electronic] United States
PMID28178690 (Publication Type: Journal Article)
Chemical References
  • Antineoplastic Agents, Phytogenic
  • Stilbenes
  • Arylsulfotransferase
  • SULT1A1 protein, human
  • Resveratrol
Topics
  • Animals
  • Antineoplastic Agents, Phytogenic (pharmacology)
  • Arylsulfotransferase (biosynthesis)
  • Cell Line, Tumor
  • Cell Proliferation (drug effects)
  • Humans
  • Rats
  • Resveratrol
  • Stilbenes (metabolism, pharmacology)
  • Urinary Bladder Neoplasms (drug therapy, pathology)

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