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However, the effect of melatonin on the growth of uterine leiomyoma is still unclear. In this study, we found that the growth of uterine leiomyoma ELT3 cells was reduced by treatment with melatonin. Treatment with melatonin increased the distribution of sub\u2010G1 phase and increased DNA condensation in ELT3 cells. Melatonin\u2010induced apoptosis and autophagy cell death progression were observed in ELT3 cells. Melatonin exerts a highly selective effect on primary normal human uterine smooth muscle (UtSMC) cells. The UtSMC cell cycle was arrested by melatonin treatment through up\u2010regulation of p21, p27, and PTEN protein expression, but melatonin did not further promote apoptosis program activation. Melatonin reduced cell proliferation in ELT3 cells underlying the activation of melatonin MT1 and MT2 receptors, which in turn down\u2010regulated the Akt\u2010ERK1\/2\u2010NF\u03baB signaling pathway. Melatonin reduced ELT3 tumor growth in both xenograft and orthotopic uterine tumor mice models. The extracellular matrix of the tumor was also reduced by melatonin treatment. Taken together, these results suggest that melatonin potentially plays a role in suppression of uterine leiomyoma growth.<\/jats:p>","DOI":"10.1111\/jpi.12620","type":"journal-article","created":{"date-parts":[[2019,11,11]],"date-time":"2019-11-11T15:04:38Z","timestamp":1573484678000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Melatonin activates cell death programs for the suppression of uterine leiomyoma cell proliferation"],"prefix":"10.1111","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2099-6258","authenticated-orcid":false,"given":"Po\u2010Han","family":"Lin","sequence":"first","affiliation":[{"name":"School of Nutrition and Health Sciences College of Nutrition Taipei Medical University Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yen\u2010Ting","family":"Tung","sequence":"additional","affiliation":[{"name":"School of Nutrition and Health Sciences 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