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.

Dexin Shen

Zhao Deng

Wei Liu

Fenfang Zhou

Yayun Fang

Danni Shan

Gang Wang

Kaiyu Qian

Mengxue Yu

Yi Zhang

Lingao Ju

Yu Xiao

Xinghuan Wang

Cell Death and Disease

《细胞死亡与分化》编辑团队为您带来的《细胞死亡与疾病》是转化细胞死亡领域的同行评审在线期刊。它旨在通过其专业（包括癌症、免疫和神经科学）促进实验和内科学的多样化和综合领域。它现在还接受一个新领域的文章：癌症代谢。

Cell Death and Disease is a peer-reviewed online journal launched by the editorial team of Cell Death and Differentiation, focusing on the field of translational cell death. The journal aims to promote diversity and integration in experimental and clinical sciences, covering specialized areas such as cancer, immunology, and neuroscience. Recently, it has also started accepting articles in the new area of cancer metabolism.

《细胞死亡与疾病》是由《细胞死亡与分化》编辑团队推出的同行评审在线期刊，专注于转化细胞死亡领域。期刊旨在促进实验科学与内科学的多样化与综合，涵盖癌症、免疫学和神经科学等专业领域。近期，期刊还开始接受关于癌症代谢的新领域文章。

Cell Death Dis

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

This study comprehensively explored the inhibitory effect of melatonin on BLCA and found that it could suppress glycolysis process and uncovered that PPARγ was a novel upstream regulator of ENO1, which mediated the downregulation of ENo1 caused by melatonin.

Category	Quartile
生物学	1
生物学, 细胞生物学	2

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

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Journal Info

Category	Quartile
CELL BIOLOGY	1