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Ramelteon, a selective MT1/MT2 receptor agonist, suppresses the proliferation and invasiveness of endometrial cancer cells

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Abstract

The incidence of endometrial cancer is increasing, making it the fifth most common cancer worldwide. To date, however, there is no standard therapy for patients with recurrent endometrial cancer. Melatonin, a hormone secreted by the pineal gland, has been shown to have anti-tumor effects in various tumor types. Although melatonin is available as a supplement, it has not been approved for cancer treatment. Ramelteon, a selective melatonin receptor type 1 and 2 (MT1/MT2) receptor agonist, has been approved to treat sleep disorders, suggesting that ramelteon may be effective in the treatment of endometrial cancer. To determine whether this agent may be effective in the treatment of endometrial cancer, this study investigated the ability of ramelteon to suppress the proliferation and invasiveness of HHUA cells, an estrogen receptor-positive endometrial cancer cell line. Ramelteon at 10−8 M maximally suppressed the proliferation of HHUA cells, reducing the percentage of Ki-67 positive proliferating cells. This effect was completely blocked by luzindole, a MT1/MT2 receptor antagonist. Furthermore, ramelteon inhibited HHUA cell invasion and reduced the expression of the MMP-2 and MMP-9 genes. These results suggested that ramelteon may be a candidate for the treatment of recurrent endometrial cancer, with activity similar to that of melatonin.

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Acknowledgements

The authors are grateful to Professor Fumie Kobayashi, Division of Tropical Diseases and Parasitology of Kyorin University School of Medicine, for kindly providing experimental facilities for this study.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo, 181-8611, Japan

    Kiyono Osanai, Yoichi Kobayashi, Tomoko Izawa & Mitsutoshi Iwashita

  2. Department of Neuroscience and Ophthalmology, Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK

    Masahiro Otsu

  3. Department of Obstetrics and Gynecology, South Miyagi Medical Center, Miyagi, Japan

    Keiji Sakai

Authors
  1. Kiyono Osanai
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  2. Yoichi Kobayashi
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  3. Masahiro Otsu
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  4. Tomoko Izawa
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  5. Keiji Sakai
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  6. Mitsutoshi Iwashita
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Correspondence to Yoichi Kobayashi.

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The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

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Osanai, K., Kobayashi, Y., Otsu, M. et al. Ramelteon, a selective MT1/MT2 receptor agonist, suppresses the proliferation and invasiveness of endometrial cancer cells. Human Cell 30, 209–215 (2017). https://doi.org/10.1007/s13577-017-0169-7

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  • DOI: https://doi.org/10.1007/s13577-017-0169-7

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