Glucuronidation and UGT isozymes in bladder: new targets for the treatment of uroepithelial carcinomas?

Vikram L. Sundararaghavan; Puneet Sindhwani; Terry D. Hinds Jr.

doi:10.18632/oncotarget.12277

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Glucuronidation and UGT isozymes in bladder: new targets for the treatment of uroepithelial carcinomas?

Vikram L. Sundararaghavan, Puneet Sindhwani and Terry D. Hinds Jr. _

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Oncotarget. 2017; 8:3640-3648. https://doi.org/10.18632/oncotarget.12277

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Abstract

Vikram L. Sundararaghavan1, Puneet Sindhwani2 and Terry D. Hinds Jr.1,2

1 Department of Physiology & Pharmacology, Center for Hypertension and Personalized Medicine, University of Toledo College of Medicine, Toledo, OH, USA

2 Department of Urology, University of Toledo College of Medicine, Toledo, OH, USA

Correspondence to:

Terry D. Hinds Jr., email:

Keywords: UGT, UDP-G glycosyltransferase, glucuronidation, bladder cancer, nuclear receptors

Received: July 22, 2016 Accepted: September 20, 2016 Published: September 27, 2016

Abstract

Bladder cancer has been linked to numerous toxins which can be concentrated in the bladder after being absorbed into the blood and filtered by the kidneys. Excessive carcinogenic load to the bladder urothelium may result in the development of cancer. However, enzymes within the bladder can metabolize carcinogens into substrates that are safer. Importantly, these proteins, namely the UGT’s (uridine 5’-diphospho-glucuronosyltransferases), have been shown to possibly prevent bladder cancer. Also, studies have shown that the UGT1 expression is decreased in uroepithelial carcinomas, which may allow for the accumulation of carcinogens in the bladder. In this review, we discuss the UGT system and its’ protective role against bladder cancer, UGT genetic mutations that modulate risk from chemicals and environmental toxins, as well as targeting of the UGT enzymes by nuclear receptors.

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Glucuronidation and UGT isozymes in bladder: new targets for the treatment of uroepithelial carcinomas?

Abstract