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Updated: Aug 4, 2025
A Murine Orthotopic Bladder Tumor Model and Tumor Detection System
Published on: January 12, 2017
Melatonin inhibits bladder tumorigenesis by suppressing PPARγ/ENO1-mediated glycolysis
Dexin Shen1, Zhao Deng1, Wei Liu2
1Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China.
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.
Insights
Melatonin suppresses bladder cancer (BLCA) by inhibiting glycolysis via ENO1, enhancing gemcitabine efficacy. This research highlights melatonin
Area of Science:
- Oncology
- Biochemistry
- Molecular Biology
Background:
- Bladder cancer (BLCA) presents significant clinical challenges due to chemoresistance.
- Melatonin, a natural hormone, exhibits potential anticancer properties.
- Investigating novel therapeutic strategies for BLCA is crucial.
Purpose of the Study:
- To explore the anticancer effects of melatonin on bladder cancer.
- To identify melatonin's downstream targets and mechanisms in BLCA.
- To assess melatonin's role in overcoming chemoresistance.
Main Methods:
- Comprehensive analysis of melatonin's effect on BLCA cell lines.
- Investigation of glycolysis pathway modulation by melatonin.
- Identification of ENO1 as a melatonin effector and PPARγ as an upstream regulator.
- Assessment of reactive oxygen species (ROS) involvement.
Main Results:
- Melatonin suppresses glycolysis in BLCA cells by downregulating ENO1.
- ENO1 acts as a predictive biomarker for BLCA.
- Melatonin or ENO1 silencing enhances gemcitabine's cytotoxic effect.
- PPARγ is identified as a novel upstream regulator of ENO1, mediating melatonin's effect.
- Melatonin's inhibitory action is mediated by excessive ROS accumulation.
Conclusions:
- Melatonin demonstrates anticancer potential in BLCA by targeting glycolysis and ENO1.
- Melatonin may serve as a therapeutic agent to overcome gemcitabine resistance in BLCA.
- ENO1 and PPARγ are key players in melatonin's anti-BLCA mechanism.
- Further clinical investigation into melatonin for BLCA chemoresistance is warranted.
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