Melatonin reduces proliferation and promotes apoptosis of bladder cancer cells by suppressing O‐GlcNAcylation of cyclin‐dependent‐like kinase 5
| Autor: | Zengqi Tan, Hongjiao Li, Liang Liang, Junjie Gou, Yazhuo Jiang, Feng Guan, Jinpeng Wu, Lulu Ning, Meixuan Lin, Xiang Li, Qilong Ma |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Proteomics
Kinase Chemistry Cyclin-dependent kinase 5 Apoptosis N-Acetylglucosaminyltransferases Cell biology carbohydrates (lipids) Melatonin Endocrinology Urinary Bladder Neoplasms nervous system Cyclins Cancer cell medicine Humans Glucose homeostasis Flux (metabolism) Cell Proliferation Cyclin medicine.drug |
| Zdroj: | Journal of Pineal Research. 71 |
| ISSN: | 1600-079X 0742-3098 |
| DOI: | 10.1111/jpi.12765 |
| Popis: | Melatonin helps to maintain circadian rhythm, exerts anticancer activity, and plays key roles in regulation of glucose homeostasis and energy metabolism. Glycosylation, a form of metabolic flux from glucose or other monosaccharides, is a common post-translational modification. Dysregulated glycosylation, particularly O-GlcNAcylation, is often a biomarker of cancer cells. In this study, elevated O-GlcNAc level in bladder cancer was inhibited by melatonin treatment. Melatonin treatment inhibited proliferation and migration and enhanced apoptosis of bladder cancer cells. Proteomic analysis revealed reduction in cyclin-dependent-like kinase 5 (CDK5) expression by melatonin. O-GlcNAc modification determined the conformation of critical T-loop domain on CDK5 and further influenced the CDK5 stability. The mechanism whereby melatonin suppressed O-GlcNAc level was based on decreased glucose uptake and metabolic flux from glucose to UDP-GlcNAc, and consequent reduction in CDK5 expression. Melatonin treatment, inhibition of O-GlcNAcylation by OSMI-1, or mutation of key O-GlcNAc site strongly suppressed in vivo tumor growth. Our findings indicate that melatonin reduces proliferation and promotes apoptosis of bladder cancer cells by suppressing O-GlcNAcylation of CDK5. |
| Databáze: | OpenAIRE |
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