Melatonin impedes prostate cancer metastasis by suppressing MMP‐13 expression
| Autor: | Tien-Huang Lin, Po-Chuan Wang, Po-Chun Chen, An-Chen Chang, Shih-Wei Wang, Liang-Wei Lin, Yi-Hsuan Chen, Huai-Ching Tai, Chih-Hsin Tang, Shiou-Sheng Chen, Yu-Wei Lai |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Cell Survival Proto-Oncogene Proteins c-jun Physiology Clinical Biochemistry Matrix metallopeptidase 13 Receptors Melatonin Down-Regulation Mice SCID Matrix metalloproteinase Models Biological p38 Mitogen-Activated Protein Kinases Metastasis Management of prostate cancer Melatonin 03 medical and health sciences Prostate cancer 0302 clinical medicine Cell Movement In vivo Cell Line Tumor Matrix Metalloproteinase 13 Animals Humans Medicine Neoplasm Invasiveness Neoplasm Metastasis Cell Death business.industry Prostatic Neoplasms Cell Biology medicine.disease 030104 developmental biology Type C Phospholipases 030220 oncology & carcinogenesis Cancer research business hormones hormone substitutes and hormone antagonists Hormone medicine.drug |
| Zdroj: | Journal of Cellular Physiology. 236:3979-3990 |
| ISSN: | 1097-4652 0021-9541 |
| DOI: | 10.1002/jcp.30150 |
| Popis: | Prostate cancer has high metastatic potential. Men with higher urinary levels of the sleep hormone melatonin are much less likely to develop advanced prostate cancer compared with men with lower levels of melatonin. Melatonin has shown anticancer activity in experimental investigations. Nevertheless, the therapeutic effect of melatonin in metastatic prostate cancer has largely remained a mystery. Analyses of Gene Expression Omnibus data and human tissue samples indicated that levels of matrix metallopeptidase 13 (MMP-13) expression are higher in prostate cancer patients than in healthy cancer-free individuals. Mechanistic investigations revealed that melatonin inhibits MMP-13 expression and the migratory and invasive capacities of prostate cancer cells via the MT1 receptor and the phospholipase C, p38, and c-Jun signaling cascades. Importantly, tumor growth rate and metastasis to distant organs were suppressed by melatonin in an orthotopic prostate cancer model. This is the first demonstration showing that melatonin impedes metastasis of prostate cancer by suppressing MMP-13 expression in both in vitro and in vivo models. Thus, melatonin is promising in the management of prostate cancer metastasis and deserves to undergo clinical investigations. |
| Databáze: | OpenAIRE |
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