Journal of Pineal Research

Volume 58, Issue 3 p. 310-320

Original Article

Melatonin-mediated Bim up-regulation and cyclooxygenase-2 (COX-2) down-regulation enhances tunicamycin-induced apoptosis in MDA-MB-231 cells

Seon Min Woo,

Seon Min Woo

Department of Immunology, School of Medicine, Keimyung University, Dalseo-Gu, Daegu, South Korea

These authors contributed equally to this work.Search for more papers by this author

Kyoung-jin Min,

Kyoung-jin Min

Department of Immunology, School of Medicine, Keimyung University, Dalseo-Gu, Daegu, South Korea

These authors contributed equally to this work.Search for more papers by this author

Taeg Kyu Kwon,

Corresponding Author

Taeg Kyu Kwon

Department of Immunology, School of Medicine, Keimyung University, Dalseo-Gu, Daegu, South Korea

Address reprint requests to Taeg Kyu Kwon, Department of Immunology, School of Medicine, Keimyung University, 2800 Dalgubeoldaero, Dalseo-Gu, Daegu 704-701, South Korea.

E-mail: [email protected]

Search for more papers by this author

Seon Min Woo,

Seon Min Woo

Department of Immunology, School of Medicine, Keimyung University, Dalseo-Gu, Daegu, South Korea

These authors contributed equally to this work.Search for more papers by this author

Kyoung-jin Min,

Kyoung-jin Min

Department of Immunology, School of Medicine, Keimyung University, Dalseo-Gu, Daegu, South Korea

These authors contributed equally to this work.Search for more papers by this author

Taeg Kyu Kwon,

Corresponding Author

Taeg Kyu Kwon

Department of Immunology, School of Medicine, Keimyung University, Dalseo-Gu, Daegu, South Korea

Address reprint requests to Taeg Kyu Kwon, Department of Immunology, School of Medicine, Keimyung University, 2800 Dalgubeoldaero, Dalseo-Gu, Daegu 704-701, South Korea.

E-mail: [email protected]

Search for more papers by this author

First published: 24 February 2015

https://doi.org/10.1111/jpi.12217

Citations: 46

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Abstract

Melatonin is involved in many physiological functions, and it has differential effects on apoptosis in normal and cancer cells. However, the mechanism of its antitumor roles is not well understood. In this study, we show that melatonin enhances tunicamycin-induced apoptosis in human breast carcinoma MDA-MB-231 cells. Melatonin up-regulates pro-apoptotic protein Bim expression at the transcriptional levels in the presence of tunicamycin. Melatonin inhibits tunicamycin-induced COX-2 expression in MDA-MB-231 cells. Furthermore, inhibition of COX-2 activity using the COX-2 inhibitor, NS398, increases tunicamycin-induced apoptosis. Interestingly, these effects were not associated with melatonin receptor signal pathways. Pertussis toxin (a general G_i protein inhibitor) or luzindole (a nonspecific melatonin receptor antagonist) did not reverse the effect of melatonin. In addition, melatonin blocked tunicamycin-induced NF-κB transcriptional activity, p65 nuclear translocation, and p38 MAPK activation. Melatonin-mediated p38 MAPK inhibition contributed to decreased COX-2 mRNA stability. Taken together, our results suggest that melatonin enhances antitumor function through up-regulation of Bim expression and down-regulation of COX-2 expression in tunicamycin-treated MDA-MB-231 cells.

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Volume58, Issue3

April 2015

Pages 310-320

Melatonin-mediated Bim up-regulation and cyclooxygenase-2 (COX-2) down-regulation enhances tunicamycin-induced apoptosis in MDA-MB-231 cells

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Melatonin-mediated Bim up-regulation and cyclooxygenase-2 (COX-2) down-regulation enhances tunicamycin-induced apoptosis in MDA-MB-231 cells

Abstract

Supporting Information

References

Citing Literature

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