Prostaglandin Reductase 1 as a Potential Therapeutic Target for Cancer Therapy.

Xing Wang,Wei Zhang,Longbin Zhang,Kunling Song,Guobing Yin,Zufeng Guo

doi:10.3389/fphar.2021.717730

Abstract

Altered tumor metabolism is a hallmark of cancer and targeting tumor metabolism has been considered as an attractive strategy for cancer therapy. Prostaglandin Reductase 1 (PTGR1) is a rate-limiting enzyme involved in the arachidonic acid metabolism pathway and mainly responsible for the deactivation of some eicosanoids, including prostaglandins and leukotriene B4. A growing evidence suggested that PTGR1 plays a significant role in cancer and has emerged as a novel target for cancer therapeutics. In this review, we summarize the progress made in recent years toward the understanding of PTGR1 function and structure, highlight the roles of PTGR1 in cancer, and describe potential inhibitors of PTGR1. Finally, we provide some thoughts on future directions that might facilitate the PTGR1 research and therapeutics development.

Highlights

Cancer is a major global burden of disease and the second leading cause of death over a period of decades (Siegel et al, 2021; Sung et al, 2021)
A growing body of literature has emphasized that metabolic enzyme Prostaglandin Reductase 1 (PTGR1) plays a significant role in cancer and is a novel potential therapeutical target for cancer treatment
One possibility is that PTGR1 might produce some metabolites, which play bigger pro-tumorigenic roles than prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) in multiple types of cancer cells, including at least triple-negative breast cancer (TNBC) and prostate cancer

Summary

Introduction

Cancer is a major global burden of disease and the second leading cause of death over a period of decades (Siegel et al, 2021; Sung et al, 2021). A growing evidence suggested that PTGR1 plays a significant role in cancer progression (Xue et al, 2016), cancer prognosis (Győrffy et al, 2013), chemotherapeutic sensitivity (Dick et al, 2004) and cancer oxidative stress (SánchezRodríguez et al, 2017). In 2010, Yue et al deposited the other unpublished structure of hPTGR1 in complex with NADP+ and raloxifene into Protein Data Bank (PDB)

Results

Conclusion