2. Academic Validation
  3. Melatonin inhibits bladder tumorigenesis by suppressing PPARγ/ENO1-mediated glycolysis

Melatonin inhibits bladder tumorigenesis by suppressing PPARγ/ENO1-mediated glycolysis

  • Cell Death Dis. 2023 Apr 6;14(4):246. doi: 10.1038/s41419-023-05770-8.
Dexin Shen # 1,  Zhao Deng # 1,  Wei Liu # 2,  Fenfang Zhou # 3,  Yayun Fang 4 5,  Danni Shan 4 5,  Gang Wang 4 5,  Kaiyu Qian 4 5,  Mengxue Yu 4 5,  Yi Zhang 6 7,  Lingao Ju 8 9,  Yu Xiao 10 11 12,  Xinghuan Wang 13 14
Affiliations

Affiliations

  • 1 Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China.
  • 2 Department of Urology, Aerospace Center Hospital, Peking University Aerospace School of Clinical Medicine, Beijing, China.
  • 3 Department of Radiology, Zhongnan Hospital of Wuhan University, Wuhan, China.
  • 4 Department of Biological Repositories, Zhongnan Hospital of Wuhan University, Wuhan, China.
  • 5 Human Genetic Resources Preservation Center of Hubei Province, Wuhan, China.
  • 6 Euler Technology, ZGC Life Sciences Park, Beijing, China.
  • 7 Center for Quantitative Biology, School of Life Sciences, Peking University, Beijing, China.
  • 8 Department of Biological Repositories, Zhongnan Hospital of Wuhan University, Wuhan, China. julingao1990@whu.edu.cn.
  • 9 Human Genetic Resources Preservation Center of Hubei Province, Wuhan, China. julingao1990@whu.edu.cn.
  • 10 Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China. yu.xiao@whu.edu.cn.
  • 11 Department of Biological Repositories, Zhongnan Hospital of Wuhan University, Wuhan, China. yu.xiao@whu.edu.cn.
  • 12 Human Genetic Resources Preservation Center of Hubei Province, Wuhan, China. yu.xiao@whu.edu.cn.
  • 13 Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China. wangxinghuan@whu.edu.cn.
  • 14 Wuhan Research Center for Infectious Diseases and Cancer, Chinese Academy of Medical Sciences, Wuhan, China. wangxinghuan@whu.edu.cn.
  • # Contributed equally.
PMID: 37024456 DOI: 10.1038/s41419-023-05770-8
Abstract

Melatonin is a well-known natural hormone, which shows a potential Anticancer effect in many human cancers. Bladder Cancer (BLCA) is one of the most malignant human cancers in the world. Chemoresistance is an increasingly prominent phenomenon that presents an obstacle to the clinical treatment of BLCA. There is an urgent need to investigate novel drugs to improve the current clinical status. In our study, we comprehensively explored the inhibitory effect of melatonin on BLCA and found that it could suppress glycolysis process. Moreover, we discovered that ENO1, a glycolytic Enzyme involved in the ninth step of glycolysis, was the downstream effector of melatonin and could be a predictive biomarker of BLCA. We also proved that enhanced glycolysis simulated by adding exogenous pyruvate could induce gemcitabine resistance, and melatonin treatment or silencing of ENO1 could intensify the cytotoxic effect of gemcitabine on BLCA cells. Excessive accumulation of Reactive Oxygen Species (ROS) mediated the inhibitory effect of melatonin on BLCA cells. Additionally, we uncovered that PPARγ was a novel upstream regulator of ENO1, which mediated the downregulation of ENO1 caused by melatonin. Our study offers a fresh perspective on the Anticancer effect of melatonin and encourages further studies on clinical chemoresistance.

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