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Melatonin resynchronizes dysregulated circadian rhythm circuitry in human prostate cancer cells.

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Melatonin resynchronizes dysregulated circadian rhythm circuitry in human prostate cancer cells.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Jung-Hynes, Brittney Huang, Wei Reiter, Russel J. Ahmad, Nihal
Description	Country affiliation: United States Author Affiliation: Jung-Hynes B ( Department of Dermatology, University of Wisconsin, Madison, WI 53706, USA.)
Abstract	Prostate cancer (PCa) is a major age-related malignancy as increasing age correlates with increased risk for developing this neoplasm. Similarly, alterations in circadian rhythms have also been associated with the aging population and cancer risk. The pineal hormone melatonin is known to regulate circadian rhythms, which is under the control of a core set of genes: Period 1, 2, 3 (Per 1-3); Cryptochrome 1, 2 (Cry 1, 2); Clock, and Bmal 1, 2. Melatonin levels have been shown to decrease in patients with cancer and exogenous melatonin exhibits antiproliferative effects against certain cancers. In this study, we challenged the hypothesis that melatonin imparts antiproliferative effects in prostate cancer via resynchronization of deregulated core clock circuitry. We found that Clock and Per2 protein levels were downregulated whereas Bmal1 protein levels were upregulated in PCa cells, compared to normal prostate cells. Additionally, employing automated quantitative analysis of a microarray containing human tissues, we found that compared to benign tissues, Clock and Per2 levels were downregulated, whereas Bmal1 levels were upregulated in PCa and other proliferative prostatic conditions. Overexpression of Per2 was found to result in a significant loss of PCa cell growth and viability. Interestingly, melatonin treatment resulted in an increase in Per2 and Clock and a reduction in Bmal1 in PCa cells. Further, melatonin treatment resulted in a resynchronization of oscillatory circadian rhythm genes (Dbp and Per2). Our data support our hypothesis and suggest that melatonin should be thoroughly investigated as an agent for the management of PCa and other age-related malignancies.
File Format	HTM / HTML
ISSN	07423098
e-ISSN	1600079X
DOI	10.1111/j.1600-079X.2010.00767.x
Journal	Journal of Pineal Research
Issue Number	1
Volume Number	49
Language	English
Publisher	Wiley
Publisher Date	2010-08-01
Publisher Place	Great Britain (UK)
Access Restriction	Open
Subject Keyword	Discipline Endocrinology Circadian Rhythm Drug Effects Melatonin Pharmacology Prostatic Neoplasms Metabolism Arntl Transcription Factors Genetics Apoptosis Blotting, Western Clock Proteins Cell Line, Tumor Dna-binding Proteins Gene Expression Gene Expression Profiling Period Circadian Proteins Poly(adp-ribose) Polymerases Reverse Transcriptase Polymerase Chain Reaction Tissue Array Analysis Transcription Factors Research Support, N.i.h., Extramural
Content Type	Text
Resource Type	Article
Subject	Endocrinology

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Melatonin resynchronizes dysregulated circadian rhythm circuitry in human prostate cancer cells

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Melatonin resynchronizes dysregulated circadian rhythm circuitry in human prostate cancer cells.

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Melatonin resynchronizes dysregulated circadian rhythm circuitry in human prostate cancer cells

Npas4 Is Activated by Melatonin, and Drives the Clock Gene Cry1 in the Ovine Pars Tuberalis

Altered diurnal variation and localization of clock proteins in the remnant kidney of 5/6 nephrectomy rats.

Nicotinamide treatment reduces the levels of histone H3K4 trimethylation in the promoter of the mper1 circadian clock gene and blocks the ability of dexamethasone to induce the acute response

Altered expression of the poly(ADP-ribosyl)ation enzymes in uveal melanoma and regulation of PARG gene expression by the transcription factor ERM.

Global analysis of transcriptional regulation by poly(ADP-ribose) polymerase-1 and poly(ADP-ribose) glycohydrolase in MCF-7 human breast cancer cells.

Mammalian circadian clock proteins form dynamic interacting microbodies distinct from phase separation.

C12orf48, termed PARP-1 binding protein, enhances poly(ADP-ribose) polymerase-1 (PARP-1) activity and protects pancreatic cancer cells from DNA damage.

Increased melatonin synthesis in pineal glands of rats in streptozotocin induced type 1 diabetes.

Melatonin resynchronizes dysregulated circadian rhythm circuitry in human prostate cancer cells.