Melatonin Inhibits EMT in Bladder Cancer by Targeting Autophagy

Sheng-Yen Hsiao; Chih-Hsin Tang; Po-Chun Chen; Tien-Huang Lin; Chia-Chia Chao

doi:10.3390/molecules27248649

Melatonin Inhibits EMT in Bladder Cancer by Targeting Autophagy

Molecules. 2022 Dec 7;27(24):8649. doi: 10.3390/molecules27248649.

Authors

Sheng-Yen Hsiao^{1

2}, Chih-Hsin Tang^{3

4

5

6

7}, Po-Chun Chen^{8

9

10}, Tien-Huang Lin^{11

12}, Chia-Chia Chao¹³

Affiliations

¹ Division of Hematology-Oncology, Department of Internal Medicine, Chi Mei Medical Center, Liouying, Tainan City 71004, Taiwan.
² Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan City 70101, Taiwan.
³ International Master Program of Biomedical Sciences, China Medical University, Taichung City 40402, Taiwan.
⁴ Graduate Institute of Biomedical Sciences, China Medical University, Taichung City 40402, Taiwan.
⁵ Department of Pharmacology, School of Medicine, China Medical University, Taichung City 40402, Taiwan.
⁶ Chinese Medicine Research Center, China Medical University, Taichung City 40402, Taiwan.
⁷ Department of Biotechnology, College of Health Science, Asia University, Taichung City 41354, Taiwan.
⁸ School of Life Science, National Taiwan Normal University, Taipei 10610, Taiwan.
⁹ Translational Medicine Center, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei 111045, Taiwan.
¹⁰ Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 40402, Taiwan.
¹¹ Department of Urology, Buddhist Tzu Chi General Hospital Taichung Branch, Taichung 427213, Taiwan.
¹² School of Post-Baccalaureate Chinese Medicine, Tzu Chi University, Hualien 97004, Taiwan.
¹³ Department of Respiratory Therapy, Fu-Jen Catholic University, New Taipei City 24205, Taiwan.

Abstract

Melatonin, a naturally biosynthesized molecule secreted by the pineal gland, exhibits antitumor activities against several different types of cancer. The mechanisms of action of melatonin against tumor progression involve cellular apoptosis, antimetastatic activity, antioxidant and mutagenic effects, antiangiogenic activity, and the restoration of cancer immune surveillance. Melatonin has anticancer activity when administered alone or in combination with standard chemotherapeutic agents, with measurable improvements seen in the clinical endpoints of tumor regression and patient survival. However, scant clinical evidence supports the use of melatonin in bladder cancer treatment. Our study has found that melatonin treatment suppresses the bladder cancer cell migratory ability by inhibiting the epithelial-mesenchymal transition (EMT) process, which appears to be linked to melatonin-induced decreases in bladder cancer cell autophagy. Finally, an evaluation of in vivo melatonin-induced antitumor effects in an orthotopic animal model of bladder cancer indicated that melatonin treatment slightly prolonged the survival of tumor-bearing mice. Our study offers novel insights into the use of melatonin in bladder cancer treatment.

Keywords: EMT; autophagy; bladder cancer; melatonin.

MeSH terms

Animals
Autophagy
Cell Line, Tumor
Epithelial-Mesenchymal Transition
Melatonin* / pharmacology
Melatonin* / therapeutic use
Mice
Signal Transduction
Urinary Bladder Neoplasms* / drug therapy

Substances

Melatonin

Grants and funding

This work was supported by grants from Chi Mei Medical Center (110-CM-FJU-04). China Medical University (CMU111-ASIA-04, CMU111-NSTC-04, CMU111-NSTC-03). China Medical University Hospital (DMR-112-146). Ministry of Science and Technology (MOST-109-2320-B-341-001).