Published on Wednesday, 06 November 2013
Molecular Mechanisms of Melatonin's Anticancer Effects
In this work - slides with video - at The New York Academy of Sciences the author, Steven M. Hill [Selected Publications] - Department of Structural & Cellular Biology, Tulane Cancer Center -, has shown that, via activation of its MT1 receptor, melatonin modulates the transcriptional activity of various nuclear receptors and the proliferation of both ERα+ and ERα- human breast cancer cells, that G alpha i2 proteins mediate the suppression of estrogen-induced ER alpha transcriptional activity by melatonin, whereas the G alpha q proteins mediate the enhancement of retinoid-induced RAR alpha transcriptional activity by melatonin and that melatonin, via repression of ROR alpha transcriptional activity, blocks the expression of the clock gene BMAL1. This video publication is divided into eight parts:
- 0'01'' - Introduction: Expression of the MT1 receptor;
- 4'51'' - MT1 associated signaling pathways: ER-alpha phosphorylation;
- 8'36'' - RAR-alpha transactivation assay;
- 10'26'' - Melatonin and 9cRA: Invasion/metastatis in breast cancer;
- 15'09'' - Melatonin and p38 MAPK: Melatonin and the MT1 receptor;
- 19'42'' - The circadian clock and breast epithelial and cancer cells;
- 22'27'' - Transcriptional activity in MCF-7 cells: SIRT1 and cancer;
- 27'13'' - Summary and acknowledgments.
With reference to video:
- Teplitzky et al. 2001: Chemoprevention of NMU-induced rat mammary carcinoma with the combination of melatonin and 9-cis-retinoic acid;
- Nowfar et al. 2002: Tumor prevention by 9-cis-retinoic acid in the N-nitroso-N-methylurea model of mammary carcinogenesis is potentiated by the pineal hormone melatonin;
- Melancon et al. 2005: Regression of NMU-induced mammary tumors with the combination of melatonin and 9-cis-retinoic acid.
- Lissoni P., L. Di Bella et al. 1987: The clinical significance of melatonin serum determination in oncological patients and its correlations with GH and PRL blood levels;
- Cos et al. 1998: Influence of melatonin on invasive and metastatic properties of MCF-7 human breast cancer cells.
- 19'52'' - 23'00'' and 24'24'' - Asher et al. 2008: SIRT1 regulates circadian clock gene expression through PER2 deacetylation (see below);
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- 20'56'' - Xiang et al. 2008: Period-2: a tumor suppressor gene in breast cancer (see below);
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- 26'11'' - Gorospe M. and De Cabo R. 2008: AsSIRTing the DNA damage response (see below).
About this publication.
About this, Hill SM et al., publication.
Selected Publications:
- Eck M, Yuan L, Duffy L, Ram PT, Ayettey S, Chen LL, Cohn CS, Reed JC, Hill SM. - A sequential treatment regimen with melatonin and all-trans retinoic acid induces apoptosis in MCF-7 tumour cells. Br J Cancer 77: 2129-2137 (1998);
- Ram PT, Kiefer T, Silverman M, Song Y, Brown GM, Hill SM. - Estrogen receptor transactivation in MCF-7 breast cancer cells by melatonin and growth factors. Mol Cell Endocrinol 141: 53-64 (1998);
- Hill SM, Teplitzky S, Ram PT, Kiefer T, Blask DE, Spriggs LL, Eck KE. - Melatonin synergizes with retinoic acid in the prevention and regression of breast cancer. Adv Exp Med Biol 460: 345-62 (1999);
- Dai J, Kiefer T, Yuan L, Hill SM. - Transcriptional repression of RORalpha activity in human breast cancer cells by melatonin. Mol Cell Endorinol 176:111-120 (2001);
- Jones FE, Burow ME, Hill SM. - Signal transduction in breast cancer: silencing the cross-talk. Eur Biopharmaceut Rev 70-73 (2003).