Abstract
A significantly increased level of the reactive oxygen species (ROS) scavenger glutathione (GSH) has been identified as a hallmark of renal cell carcinoma (RCC). The proposed mechanism for increased GSH levels is to counteract damaging ROS to sustain the viability and growth of the malignancy. Here, we review the current knowledge about the three main RCC subtypes, namely clear cell RCC (ccRCC), papillary RCC (pRCC), and chromophobe RCC (chRCC), at the genetic, transcript, protein, and metabolite level and highlight their mutual influence on GSH metabolism. A further discussion addresses the question of how the manipulation of GSH levels can be exploited as a potential treatment strategy for RCC.
Highlights
Increased reactive oxygen species (ROS) levels, including the superoxide anion, hydrogen peroxide, and hydroxyl radical, have been reported in many different cancer types
We review the current knowledge about the three main renal cell carcinoma (RCC) subtypes, namely clear cell RCC, papillary RCC, and chromophobe RCC, at the genetic, transcript, protein, and metabolite level and highlight their mutual influence on GSH metabolism
The de novo biosynthesis of GSH involves two ATP-dependent enzymatic reactions: The first step is catalyzed by glutamate cysteine ligase (GCL), which ligates the amino group of cysteine to the γ-carboxylate of glutamic acid to form the dipeptide γ-glutamyl cysteine
Summary
Increased reactive oxygen species (ROS) levels, including the superoxide anion, hydrogen peroxide, and hydroxyl radical, have been reported in many different cancer types. Glutathione (GSH), a tripeptide thiol antioxidant composed of the amino acids glutamic acid, cysteine, and glycine [2], is the main ROS scavenger in cells. Massive ROS accumulations can limit by causing severe damage of biomolecules, canwhich lead to cell death [13].toAs cancer growth by oxidative causing severe oxidative damage ofwhich biomolecules, can lead cella consequence, cancer cells are required to deliberately balance the levels of and antioxidants Cancer cells are required to deliberately balance the levels of ROS and GSH) to maintain redox homeostasis, which sustains viabilitywhich and growth. We ROS will focus on the role of the ROS scavenger GSH in RCC and discuss possible supplementation with inhibitors strategies that can potentially exploit of scavenger.
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