title: Melatonin affects voltage-dependent calcium and potassium currents in MCF-7 cell line cultured either in growth or differentiation medium.
abstract: 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+) currents (T- and L-type), outward delayed rectifier K(+) 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.
authors.affiliation: Department of Experimental and Clinical Medicine, Section of Physiological Sciences, University of Florence, 50134 Florence, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Squecco
authors.affiliation: Department of Experimental and Clinical Medicine, Section of Anatomy and Histology, University of Florence, 50134 Florence, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Tani
authors.affiliation: Department of Experimental and Clinical Medicine, Section of Physiological Sciences, University of Florence, 50134 Florence, Italy.
authors.forename: Sandra
authors.initials: S
authors.lastname: Zecchi-Orlandini
authors.affiliation: Department of Experimental and Clinical Medicine, Section of Anatomy and Histology, University of Florence, 50134 Florence, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Formigli
authors.affiliation: Department of Experimental and Clinical Medicine, Section of Physiological Sciences, University of Florence, 50134 Florence, Italy. Electronic address: fabio.francini@unifi.it.
authors.forename: Fabio
authors.initials: F
authors.lastname: Francini
mesh_terms: D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D006801:Humans; D061986:MCF-7 Cells; D008550:Melatonin / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects*; D015221:Potassium Channels / Q000378:metabolism*
chemical_list: D015220:Calcium Channels; D017077:Culture Media, Conditioned; D015221:Potassium Channels; D008550:Melatonin; D002118:Calcium
keywords: Chromanol (PubChem CID: 92890); Electrophysiology; Iberiotoxin (PubChem CID: 16132435); Melatonin; Melatonin (PubChem CID: 896); Nifedipine (PubChem CID: 4485); Voltage-dependent Ca(2+) currents; Voltage-dependent K(+) currents; α-Dendrotoxin (PubChem SID: 135651983)