Membrane‐bound melatonin receptor MT1 down‐regulates estrogen responsive genes in breast cancer cells

Girgert, Rainer; Hanf, Volker; Emons, Günter; Gründker, Carsten

doi:10.1111/j.1600-079x.2009.00684.x

Cited by 61 publications

(57 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Extrapineal sites contribute poorly, or only upon specific stimuli to circulating melatonin [1]. Melatonin influences numerous physiological actions that may be mediated by the binding of the indoleamine to membrane receptors in all tissues [2,3]. Due to its excellent lipophilic properties, melatonin is able to enter the subcellular compartment, finding it in high concentrations in the nucleus and the mitochondria of cells [4,5], being capable to bind to some cytosolic proteins like kinase-C [6], calmodulin [7] and calreticulin [8].…”

Section: Introductionmentioning

confidence: 99%

Melatonin: A Review of Its Potential Functions and Effects on Dental Diseases

Permuy

López-Peña

González‐Cantalapiedra

et al. 2017

IJMS

View full text Add to dashboard Cite

Melatonin is a hormone synthesised and secreted by the pineal gland and other organs. Its secretion, controlled by an endogenous circadian cycle, has been proven to exert immunological, anti-oxidant, and anti-inflammatory effects that can be beneficial in the treatment of certain dental diseases. This article is aimed at carrying out a review of the literature published about the use of melatonin in the dental field and summarising its potential effects. In this review article, an extensive search in different databases of scientific journals was performed with the objective of summarising all of the information published on melatonin use in dental diseases, focussing on periodontal diseases and dental implantology. Melatonin released in a natural way into the saliva, or added as an external treatment, may have important implications for dental disorders, such as periodontal disease, as well as in the osseointegration of dental implants, due to its anti-inflammatory and osseoconductive effects. Melatonin has demonstrated to have beneficial effects on dental pathologies, although further research is needed to understand the exact mechanisms of this molecule.

show abstract

Section: Introductionmentioning

confidence: 99%

Melatonin: A Review of Its Potential Functions and Effects on Dental Diseases

Permuy

López-Peña

González‐Cantalapiedra

et al. 2017

IJMS

View full text Add to dashboard Cite

show abstract

“…Since Ca 2 þ seems to be a crucial regulator of the cell cycle necessary for proper proliferation (Bertolesi et al, 2002;Gray et al, 2004;Naziroğlu et al, 2012;Wang et al, 2000), the associated reduction of free [Ca 2 þ ] i observed in our experiments supports the clue that melatonin may contribute to the decline of proliferation also disturbing internal Ca 2 þ homeostasis. The G-protein-coupled melatonin MT1 receptors are expressed in MCF-7 cells (Girgert et al, 2009;Hill et al, 2011b;Jablonska et al, 2013;Jawed et al, 2007;Rich et al, 1999) and, via the inhibition of adenylate cyclase activity (Jablonska et al, 2013;Jawed et al, 2007), their activation leads to the decrease of adenosine 3 0 , 5 0 -cyclic monophosphate (cAMP) synthesis. Considering that in MCF-7 melatonin affected cell functionality by a significant depletion of ATP levels (Margheri et al, 2012), we propose that the decrease of cAMP, leading to a decrease of PKA activity and channel phosphorylation, can be considered a crucial mechanism involved in the reduction of L-and T-type Ca 2 þ currents (Mahapatra et al, 2012;Novara et al, 2004;Sundelacruz et al, 2009), further stressing the evidence that Ca 2 þ channels are a target by which melatonin can modulate cell proliferation.…”

Section: Ctrmentioning

confidence: 99%

“…Moreover, preclinical in vitro and in vivo studies and clinical trials showed that melatonin was able to exert an oncostatic action on different tumors (Girgert et al, 2009;Hill et al, 2009Hill et al, , 2011aJung and Ahmad, 2006;Sánchez-Barceló et al, 2012;Srinivasan et al, 2008), to increase the efficacy of chemotherapy when used in adjuvant settings and to decrease the side effects (Vijayalaxmi et al, 2002). Since proliferation and differentiation are typical of any cell system and are carefully regulated in the course of physiological development and life cycle, tumor evolution must imply a deregulation of their morphofunctional features.…”

Section: Introductionmentioning

confidence: 99%

“…In particular, by electrophysiological technique, we evaluated the action of melatonin on resting membrane potential and on voltage-dependent ionic channels known to play a role in proliferation (Baglioni et al, 2012;Bertolesi et al, 2002;Currò, 2014;Enomoto et al, 1986;Gamper et al, 2002;Girgert et al, 2009;Grant et al, 2009;Gray et al, 2004;Haren et al, 2010;Kunzelmann, 2005).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Melatonin affects voltage-dependent calcium and potassium currents in MCF-7 cell line cultured either in growth or differentiation medium

Squecco

Tani

Zecchi‐Orlandini

et al. 2015

European Journal of Pharmacology

View full text Add to dashboard Cite

Chemical compounds studied in this article:α-Dendrotoxin (PubChem SID: 135651983) Chromanol (PubChem CID: 92890) Iberiotoxin (PubChem CID: 16132435) Melatonin (PubChem CID: 896) Nifedipine (PubChem CID: 4485) a b s t r a c t Big efforts have been dedicated up to now to identify novel targets for cancer treatment. The peculiar biophysical profile and the atypical ionic channels activity shown by diverse types of human cancers suggest that ion channels may be possible targets in cancer therapy. Earlier studies have shown that melatonin exerts an oncostatic action on different tumors. In particular, it was shown that melatonin was able to inhibit growth/viability and proliferation, to reduce the invasiveness and metastatic properties of human estrogen-sensitive breast adenocarcinoma MCF-7 cell line cultured in growth medium, with substantial impairments of epidermal growth factor (EGF) and Notch-1-mediated signaling. The purpose of this work was to evaluate on MCF-7 cells the possible effects of melatonin on the biophysical features known to have a role in proliferation and differentiation, by using the patch-clamp technique. Our results show that in cells cultured in growth as well as in differentiation medium melatonin caused a hyperpolarization of resting membrane potential paralleled by significant changes of the inward Ca 2 þ currents (T-and L-type), outward delayed rectifier K þ currents and cell capacitance. All these effects are involved in MCF-7 growth and differentiation. These findings strongly suggest that melatonin, acting as a modulator of different voltage-dependent ion channels, might be considered a new promising tool for specifically disrupting cell viability and differentiation pathways in tumour cells with possible beneficial effects on cancer therapy.

show abstract

“…We were able to show that the breast cancer susceptibility gene BRCA-1 is a good candidate to study cross-talk between ER and melatonin signal transduction [Girgert et al, 2009]. BRCA-1 expression is upregulated by estradiol, because the BRCA-1 promoter contains an AP-1 instead of an estrogen receptor element [Webb et al, 1999].…”

Section: Introductionmentioning

confidence: 99%

Signal transduction of the melatonin receptor MT1 is disrupted in breast cancer cells by electromagnetic fields

Girgert

Hanf

Emons

et al. 2009

Bioelectromagnetics

Self Cite

View full text Add to dashboard Cite

The growth of estrogen-receptor positive breast cancer cells is inhibited by the pineal gland hormone, melatonin. Concern has been raised that power-line frequency and microwave electromagnetic fields (EMFs) could reduce the efficiency of melatonin on breast cancer cells. In this study we investigated the impact of EMFs on the signal transduction of the high-affinity receptor MT1 in parental MCF-7 cells and MCF-7 cells transfected with the MT1 gene. The binding of the cAMP-responsive element binding (CREB) protein to a promoter sequence of BRCA-1 after stimulation with melatonin was analyzed by a gel-shift assay and the expression of four estrogen-responsive genes was measured in sham-exposed breast cancer cells and cells exposed to a sinusoidal 50 Hz EMF of 1.2 microT for 48 h. In sham-exposed cells, binding of CREB to the promoter of BRCA-1 was increased by estradiol and subsequently diminished by treatment with melatonin. In cells exposed to 1.2 microT, 50 Hz EMF, binding of CREB was almost completely omitted. Expression of BRCA-1, p53, p21(WAF), and c-myc was increased by estradiol stimulation and subsequently decreased by melatonin treatment in both cell lines, except for p53 expression in the transfected cell line, thereby proving the antiestrogenic effect of melatonin at molecular level. In contrast, in breast cancer cells transfected with MT1 exposed to 1.2 microT of the 50 Hz EMF, the expression of p53 and c-myc increased significantly after melatonin treatment but for p21(WAF) the increase was not significant. These results convincingly prove the negative effect of EMF on the antiestrogenic effect of melatonin in breast cancer cells.

show abstract

Membrane‐bound melatonin receptor MT1 down‐regulates estrogen responsive genes in breast cancer cells

Cited by 61 publications

References 28 publications

Melatonin: A Review of Its Potential Functions and Effects on Dental Diseases

Melatonin: A Review of Its Potential Functions and Effects on Dental Diseases

Melatonin affects voltage-dependent calcium and potassium currents in MCF-7 cell line cultured either in growth or differentiation medium

Signal transduction of the melatonin receptor MT1 is disrupted in breast cancer cells by electromagnetic fields

Contact Info

Product

Resources

About