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Ramelteon, a selective MT1/MT2 receptor agonist, suppresses the proliferation and invasiveness of endometrial cancer
Kiyono Osanai1, Yoichi Kobayashi2, Masahiro Otsu3
1Department of Obstetrics and Gynecology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo, 181-8611, Japan.
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.
Insights
Ramelteon, a melatonin receptor agonist, suppressed endometrial cancer cell proliferation and invasion. This suggests ramelteon may be a potential treatment for recurrent endometrial cancer.
Area of Science:
- Oncology
- Endocrinology
Background:
- Endometrial cancer incidence is rising globally, with no standard therapy for recurrent cases.
- Melatonin exhibits anti-tumor properties, but is not approved for cancer treatment.
- Ramelteon, a selective melatonin receptor agonist, is approved for sleep disorders.
Purpose of the Study:
- To investigate ramelteon's efficacy in suppressing endometrial cancer cell proliferation and invasion.
- To evaluate ramelteon's potential as a therapeutic agent for recurrent endometrial cancer.
Main Methods:
- Utilized HHUA cells, an estrogen receptor-positive endometrial cancer cell line.
- Assessed ramelteon's effect on cell proliferation (Ki-67) and invasion.
- Investigated the role of melatonin receptors (MT1/MT2) using luzindole antagonist.
- Quantified expression of MMP-2 and MMP-9 genes.
Main Results:
- Ramelteon (10-8 M) maximally suppressed HHUA cell proliferation, reducing Ki-67 positive cells.
- The anti-proliferative effect was fully blocked by the MT1/MT2 receptor antagonist luzindole.
- Ramelteon inhibited HHUA cell invasion and decreased MMP-2 and MMP-9 gene expression.
Conclusions:
- Ramelteon demonstrates anti-proliferative and anti-invasive activity in an endometrial cancer cell line.
- These findings suggest ramelteon could be a candidate for treating recurrent endometrial cancer.
- Ramelteon's activity may be mediated through MT1/MT2 receptors, similar to melatonin.