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Published on: February 21, 2014
Expression of melatonin receptor (MT1) and interaction between melatonin and estrogen in endometrial cancer cell line
Mari Watanabe1, Yoichi Kobayashi, Noriyuki Takahashi
1Department of Obstetrics and Gynecology, St Marianna University School of Medicine, Kanagawa, Japan.
Aim:
To determine the receptor subtypes of melatonin in estrogen receptor-positive endometrial cancer cell line, Ishikawa, and the influence of melatonin on chemosensitivity.
Methods:
To confirm the subtype of melatonin on Ishikawa cells, cells were treated with melatonin alone and with antagonists against melatonin receptor luzindole and 4-phenyl-2-propionamidotetralin (4-P-PDOT). Expression of MT1/MT2 mRNA was analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR). Immunocytochemistry of MT1/MT2 was also performed. The effect of melatonin against expression of MT1, MT2, and ERalpha-receptors mRNA was compared with RT-PCR. To determine whether melatonin enhances the effect of anticancer agents, chemosensitivity test was performed with or without melatonin.
Results:
Our study revealed that Ishikawa cells express MT1 by both RT-PCR and immunocytochemistry. In contrast, expression of MT2 mRNA was not found. Furthermore, ERalpha mRNA expression was attenuated at melatonin level of 1 x 10(-9) M. Chemosensitivity test revealed that melatonin enhanced anti-tumor effects of paclitaxel among anticancer drugs tested.
Conclusion:
Based on the above results, MT1 receptor, but not MT2, is expressed in Ishikawa cells. It was also revealed that the cytostatic effect of melatonin is partly an action mediated by MT1 receptor, and attenuation of ERalpha expression was predicted as the mechanism of action. Clinical application of melatonin to biochemotherapy might be also expected.
Insights
Melatonin primarily acts through the MT1 receptor in Ishikawa endometrial cancer cells, reducing estrogen receptor alpha expression and enhancing paclitaxel
Area of Science:
- Endocrinology
- Oncology
- Molecular Biology
Background:
- Estrogen receptor-positive endometrial cancer is a significant health concern.
- Melatonin's role in cancer is complex and warrants further investigation.
- Understanding melatonin receptor subtypes is crucial for targeted therapies.
Purpose of the Study:
- To identify melatonin receptor subtypes in the Ishikawa endometrial cancer cell line.
- To investigate the impact of melatonin on chemosensitivity in this cell line.
- To elucidate the mechanism of melatonin's action on estrogen receptor expression.
Main Methods:
- Melatonin receptor subtype confirmation using RT-PCR and immunocytochemistry.
- Treatment with melatonin and specific receptor antagonists (luzindole, 4-P-PDOT).
- Assessment of melatonin's effect on MT1, MT2, and ERalpha mRNA expression.
- Chemosensitivity testing with paclitaxel in the presence and absence of melatonin.
Main Results:
- Ishikawa cells exclusively express the MT1 melatonin receptor mRNA and protein.
- Melatonin treatment significantly attenuated estrogen receptor alpha (ERalpha) mRNA expression.
- Melatonin enhanced the anti-tumor efficacy of paclitaxel in chemosensitivity tests.
Conclusions:
- The MT1 receptor mediates melatonin's cytostatic effects in Ishikawa cells.
- Attenuation of ERalpha expression is a key mechanism by which melatonin exerts its effects.
- Melatonin holds potential for clinical application in biochemotherapy for endometrial cancer.

