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Review
. 2017 Jan 10;8(2):3640-3648.
doi: 10.18632/oncotarget.12277.

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

Vikram L Sundararaghavan  1 , Puneet Sindhwani  2 , Terry D Hinds Jr  1   2
Affiliations
Review

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

Vikram L Sundararaghavan et al. Oncotarget. .

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.

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

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Conflict of interest statement

Conflicts of Interest

The authors declare that there is no conflict of interests regarding the publication of this paper.

Figures

Figure 1
Figure 1. Function of UGT in Normal and Bladder Cancer
A. In normal bladder toxins (green) undergo glucuronidation by UGTs (red) with glucuronic acid (GA) to form safer metabolites (gray) that are excreted. B. In bladder cancer glucuronidation of toxins are reduced due to the lower expression of UGTs, which causes an accumulation of toxins and development of uroepithelial carcinomas.
Figure 2
Figure 2. UGT Superfamily
The different isoforms of the human UGT superfamily based upon differential splicing of the RNA transcripts. Additionally, tissue expression data of the different isoforms are listed. Psueudogenes are not included. Pleases note that information for this diagram was obtained from the following [11, 13] and modified into a graphical representation.
Figure 3
Figure 3. Nuclear Receptor Regulation of UGT
Nuclear receptors that increase UGT expression are labeled in green and in red for inhibitory receptors. The ligands of each nuclear receptor is labeled in gray. E2, estradiol; GCs, glucocorticoids; BBN, N-butyl-N-(4-hydroxybutyl)nitrosamine; 2AI, 2,2’-aminophenyl indole; DHT, dihydrotestosterone.
See this image and copyright information in PMC

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