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

Abstract

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.

Melatonin Reduces Excitability in Dorsal Root Ganglia Neurons with Inflection on the Repolarization Phase of the Action Potential

“…Concerning the passive electrophysiological properties of the neurons, we observed a hyperpolarization of the RMP after melatonin exposure. This hyperpolarization effect, caused by melatonin, was reported in several works [21,22,23]. Although this effect was similar to that previously described [15], the magnitude of the hyperpolarization showed a tendency to be greater in N inf neurons.…”

Melatonin, an inhibitory agent in breast cancer

“…The melatonin MT1-dependent anti proliferative actions could be attributed to several mechanisms, including repression of estrogen and ERa transcription, Aromatase down regulation, disruption in internal ca 2? hemostasis [58], the ribosome biogenesis suppression [59], inhibition of cAMP formation, induction of p53, and p21 upregulation. Additionally it seems that the suppression of linoleic acid uptake and its conversion to 13-hydroxyoctadexadienoic acid (13-HODE), associated with the reduction of breast cancer cells metabolism through melatonin treatment may boost the melatonin anti proliferative effects [12,29,60].…”

Application of a validated HPLC-PDA method for the determination of melatonin content and its release from poly(lactic acid) nanoparticles

“…The role of MLT as a neuroprotective agent against diseases as Parkinson's and Alzheimer's and in brain lesions from different etiology, such as ischemia and intracerebral hemorrhage, has been suggested [2] , [6] , [8] . Furthermore, the administration of exogenous MLT in pharmacological doses can also to exert cytotoxicity in tumor cells such as breast adenocarcinoma MCF-7, human osteosarcoma and gastrointestinal tract tumors [9] , [10] , [11] . Therefore, considering the natural decline of MLT and its potential therapeutic effects, the exogenous administration of this molecule might be useful.…”