Light at night and melatonin have opposite effects on breast cancer tumors in mice assessed by growth rates and global DNA methylation

Schwimmer, Hagit; Metzer, Avishag; Pilosof, Yonit; Szyf, Moshe; Machnes, Ziv; Fares, Fuad; Harel, Orna; Haim, Abraham

doi:10.3109/07420528.2013.842925

Cited by 73 publications

(86 citation statements)

References 36 publications

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“…In support of this finding, ALAN exposure as low as 0.2 lux has been demonstrated to be sufficient to induce tumor growth and increase tumor lipid uptake and metabolism [159]. In female Balb/c mice 4T1 mammary carcinoma model, tumor growth clearly accelerated in response to 1X30 min/ day ALAN exposure (white fluorescent, 450 Lux, 469 nm) for 21 days compared with mice maintained under the same conditions, but without ALAN [145]. ALAN affected 4T1 tumor growth in a wavelength-dependent manner.…”

Section: Circadian Disruption and Breast Cancersupporting

confidence: 50%

“…In mice inoculated with 4T1 breast cancer cells, ALAN exposure has been associated with the promotion of tumor growth compared with unexposed mice [145,160]. In these recent studies, the addition of MLT to the drinking water blocked the accelerated tumor growth effects of ALAN.…”

Section: Mlt and Cancermentioning

confidence: 97%

“…Furthermore, in estrogen-receptor-related breast cancer, MLT has been found to decrease expression levels of the aromatase gene (CYP19), which are responsible for the activity status of estrogens plausibly via methylation of the CYP19 gene or deacetylation of CYP19 histone at the promotor level [109]. Under both blue-LED and florescent ALAN exposures, Blab/c 4T1 breast-cancer cell tumor-inoculated female mice clearly demonstrated decreased GDM levels and increased tumor growth rates, and both were reversed by the addition of MLT to the drinking water during nighttime [145,160]. Overall, these findings suggest that MLT can induce epigenetic modifications of several metabolicand carcinogenic-related genes, subsequently rendering them active or inactive by histone acetylation or DNA methylation.…”

Section: Mlt and Epigenetic Modificationsmentioning

confidence: 99%

“…ALAN exposure as a prevailing feature of our modern 24/7 (h/days) active society is recognized as the most powerful factor, behind circadian disruption [138-140; Figure 2]. The evidence for a causal and direct association between ALAN-induced circadian disruption and breast cancer development comes primarily from both epidemiological observations [141][142][143] and experimental studies [144][145][146].…”

Section: Circadian Disruption and Breast Cancermentioning

confidence: 99%

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Artificial light-at-night – a novel lifestyle risk factor for metabolic disorder and cancer morbidity

Zubidat

Haim

2017

Journal of Basic and Clinical Physiology and Pharmacology

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Both obesity and breast cancer are already recognized worldwide as the most common syndromes in our modern society. Currently, there is accumulating evidence from epidemiological and experimental studies suggesting that these syndromes are closely associated with circadian disruption. It has been suggested that melatonin (MLT) and the circadian clock genes both play an important role in the development of these syndromes. However, we still poorly understand the molecular mechanism underlying the association between circadian disruption and the modern health syndromes. One promising candidate is epigenetic modifications of various genes, including clock genes, circadian-related genes, oncogenes, and metabolic genes. DNA methylation is the most prominent epigenetic signaling tool for gene expression regulation induced by environmental exposures, such as artificial light-at-night (ALAN). In this review, we first provide an overview on the molecular feedback loops that generate the circadian regulation and how circadian disruption by ALAN can impose adverse impacts on public health, particularly metabolic disorders and breast cancer development. We then focus on the relation between ALAN-induced circadian disruption and both global DNA methylation and specific loci methylation in relation to obesity and breast cancer morbidities. DNA hypo-methylation and DNA hyper-methylation, are suggested as the most studied epigenetic tools for the activation and silencing of genes that regulate metabolic and monostatic responses. Finally, we discuss the potential clinical and therapeutic roles of MLT suppression and DNA methylation patterns as novel biomarkers for the early detection of metabolic disorders and breast cancer development.

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Section: Circadian Disruption and Breast Cancersupporting

confidence: 50%

Section: Mlt and Cancermentioning

confidence: 97%

Section: Mlt and Epigenetic Modificationsmentioning

confidence: 99%

Section: Circadian Disruption and Breast Cancermentioning

confidence: 99%

See 2 more Smart Citations

Artificial light-at-night – a novel lifestyle risk factor for metabolic disorder and cancer morbidity

Zubidat

Haim

2017

Journal of Basic and Clinical Physiology and Pharmacology

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“…One of these approaches had considered the assumed tumor-promoting effects of LAN. When 4T1 breast cancer cells were inoculated into BALB/c mice, tumor growth was favored by LAN, along with changes in the global DNA methylation pattern, effects that were reported to be partially reversed by melatonin [62]. The reversal was reportedly associated with reduced growth rates of breast tumors.…”

Section: Chromatin Remodeling By Circadian Oscillators and Melatoninmentioning

confidence: 96%

Untitled

2017

J Geriatr Med Gerontol

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Melatonin is a highly pleiotropic regulator molecule that influences numerous functions in many cell types. Its actions comprise direct and circadian oscillator-mediated effects. The levels of circulating melatonin typically decline in the course of aging. Additionally,various aging-associated diseases further decrease melatonin concentrations. With regard to its remarkably broad spectrum of actions, control mechanisms upstream and downstream of melatonin should be investigated much more in detail with regard to the contribution of epigenetic modulation. The importance of epigenetic alterations has already become evident in the fields of both gerontology and chronobiology. Therefore, it seems necessary to fill the gaps concerning corresponding processes related to melatonin, especially under the aspects of physiologic malfunctions because of aging-associated decreases of melatonin. This review outlines the findings on melatonin's epigenetic actions, as obtained to date, and sets these results in correspondence to general knowledge and many specific findings concerning circadian rhythms. These considerations focus on DNA methylation and erasure of 5-methylcytosine, on histone modification, in particular, acetylation/deacetylation and methylation/demethylation, and on the manifold roles of noncoding RNAs, especially microRNAs. With regard to melatonin's spectrum of actions in the gerontological context, emphasis is given to its contribution to circadian oscillation amplitudes, to anti-inflammatory actions and to antioxidative protection.

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Melatonin‐induced increase of lipid droplets accumulation and in vitro maturation in porcine oocytes is mediated by mitochondrial quiescence

Yin

Gong

et al. 2017

Journal Cellular Physiology

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Melatonin, the major pineal secretory product, has a significant impact on the female reproductive system. Recently, the beneficial effects of melatonin on mammalian oocyte maturation and embryonic development have drawn increased attention. However, the exact underlying mechanisms remain to be fully elucidated. This study demonstrates that supplementing melatonin to in vitro maturation (IVM) medium enhances IVM rate, lipid droplets (LDs) accumulation as well as triglyceride content in porcine oocytes. Decrease of mitochondrial membrane potential, mitochondrial respiratory chain complex IV activity as well as mitochondrial reactive oxygen species (mROS) content indicated that melatonin induced a decrease of mitochondrial activity. The copy number of mitochondrial DNA (mtDNA) which encodes essential subunits of oxidative phosphorylation (OXPHOS), was not affected by melatonin.However, the expression of mtDNA-encoded genes was significantly down-regulated after melatonin treatment. The DNA methyltransferase DNMT1, which regulates methylation and expression of mtDNA, was increased and translocated into the mitochondria in melatonintreated oocytes. The inhibitory effect of melatonin on the expression of mtDNA was significantly prevented by simultaneous addition of DNMT1 inhibitor, which suggests that melatonin regulates the transcription of mtDNA through up-regulation of DNMT1 and mtDNA methylation.Increase of triglyceride contents after inhibition of OXPHOS indicated that mitochondrial quiescence is crucial for LDs accumulation in oocytes. Taken together, our results suggest that melatonin-induced reduction in mROS production and increase in IVM, and LDs accumulation in porcine oocytes is mediated by mitochondrial quiescence. K E Y W O R D SDNA methyltransferase 1, in vitro maturation, melatonin, mitochondrial quiescence, oocyte

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Light at night and melatonin have opposite effects on breast cancer tumors in mice assessed by growth rates and global DNA methylation

Cited by 73 publications

References 36 publications

Artificial light-at-night – a novel lifestyle risk factor for metabolic disorder and cancer morbidity

Artificial light-at-night – a novel lifestyle risk factor for metabolic disorder and cancer morbidity

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Melatonin‐induced increase of lipid droplets accumulation and in vitro maturation in porcine oocytes is mediated by mitochondrial quiescence

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