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Cancer Cell International
Published in: Cancer Cell International 1/2016

Open Access 01-12-2016 | Primary research

Altering bioelectricity on inhibition of human breast cancer cells

Authors: Seher Berzingi, Mackenzie Newman, Han-Gang Yu

Published in: Cancer Cell International | Issue 1/2016

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Abstract

Background

Membrane depolarization is associated with breast cancer. Depolarization-activated voltage-gated ion channels are directly implicated in the initiation, proliferation, and metastasis of breast cancer.

Methods

In this study, the role of voltage-gated potassium and calcium ion channel modulation was explored in two different invasive ductal human carcinoma cell lines, MDA-MB-231 (triple-negative) and MCF7 (estrogen-receptor-positive).

Results

Resting membrane potential is more depolarized in MCF7 and MDA-MB-231 cells compared to normal human mammary epithelial cells. Increasing extracellular potassium concentration up to 50 mM depolarized membrane potential and greatly increased cell growth. Tetraethylammonium (TEA), a non-specific blocker of voltage-gated potassium channels, stimulated growth of MCF7 cells (control group grew by 201 %, 1 mM TEA group grew 376 %). Depolarization-induced calcium influx was hypothesized as a requirement for growth of human breast cancer. Removing calcium from culture medium stopped growth of MDA and MCF7 cells, leading to cell death after 1 week. Verapamil, a blocker of voltage-gated calcium channels clinically used in treating hypertension and coronary disease, inhibited growth of MDA cells at low concentration (10–20 μM) by 73 and 92 % after 1 and 2 days, respectively. At high concentration (100 μM), verapamil killed >90 % of MDA and MCF7 cells after 1 day. Immunoblotting experiments demonstrated that an increased expression of caspase-3, critical in apoptosis signaling, positively correlated with verapamil concentration in MDA cells. In MCF7, caspase-9 expression is increased in response to verapamil.

Conclusions

Our results support our hypotheses that membrane depolarization and depolarization-induced calcium influx stimulate proliferation of human breast cancer cells, independently of cancer subtypes. The underlying mechanism of verapamil-induced cell death involves different caspases in MCF7 and MDA-MB-231. These data suggest that voltage-gated potassium and calcium channels may be putative targets for pharmaceutical remediation in human invasive ductal carcinomas.
Literature
1.
Holliday DL, Speirs V. Choosing the right cell line for breast cancer research. Breast Cancer Res. 2011;13(4):1–7.CrossRef
2.
Lacroix M, Leclercq G. Relevance of breast cancer cell lines as models for breast tumours: an update. Breast Cancer Res Treat. 2004;83(3):249–89.CrossRefPubMed
3.
Gozgit JM, Pentecost BT, Marconi SA, Otis CN, Wu C, Arcaro KF. Use of an aggressive MCF-7 cell line variant, TMX2-28, to study cell invasion in breast cancer. Mol Cancer Res. 2006;4(12):905–13.CrossRefPubMed
4.
Levin M. Molecular bioelectricity in developmental biology: new tools and recent discoveries: control of cell behavior and pattern formation by transmembrane potential gradients. BioEssays. 2012;34(3):205–17.CrossRefPubMedPubMedCentral
5.
Prevarskaya N, Skryma R, Shuba Y. Ion channels and the hallmarks of cancer. Trends Mol Med. 2010;16(3):107–21.CrossRefPubMed
6.
Fraser SP, Pardo LA. Ion channels: functional expression and therapeutic potential in cancer. Colloquium on Ion channels and cancer. EMBO Rep. 2008;9(6):512–5.CrossRefPubMedPubMedCentral
7.
Djamgoz MB, Coombes RC, Schwab A. Ion transport and cancer: from initiation to metastasis. Philos Trans R Soc Lond B Biol Sci. 2014;369(1638):20130092.CrossRefPubMedPubMedCentral
8.
Arcangeli A, Crociani O, Lastraioli E, Masi A, Pillozzi S, Becchetti A. Targeting ion channels in cancer: a novel frontier in antineoplastic therapy. Curr Med Chem. 2009;16(1):66–93.CrossRefPubMed
9.
Cuddapah VA, Sontheimer H. Ion channels and transporters [corrected] in cancer. 2. Ion channels and the control of cancer cell migration. Am J Physiol Cell Physiol. 2011;301(3):C541–9.CrossRefPubMedPubMedCentral
10.
Marino AA, Iliev IG, Schwalke MA, Gonzalez E, Marler KC, Flanagan CA. Association between cell membrane potential and breast cancer. Tumour Biol. 1994;15(2):82–9.CrossRefPubMed
11.
Azimi I, Roberts-Thomson SJ, Monteith GR. Calcium influx pathways in breast cancer: opportunities for pharmacological intervention. Br J Pharmacol. 2014;171(4):945–60.CrossRefPubMedPubMedCentral
12.
Coogan PF. Calcium-channel blockers and breast cancer: a hypothesis revived. JAMA Int Med. 2013;173(17):1637–8.CrossRef
13.
Taylor JT, Huang L, Pottle JE, Liu K, Yang Y, Zeng X, Keyser BM, Agrawal KC, Hansen JB, Li M. Selective blockade of T-type Ca2+ channels suppresses human breast cancer cell proliferation. Cancer Lett. 2008;267(1):116–24.CrossRefPubMed
14.
Alkadhi KA, Simples JE Jr. Effects of inorganic potassium channel blockers on calcium requirement of transmission in a sympathetic ganglion. J Auton Nerv Syst. 1991;34(2–3):221–9.CrossRefPubMed
15.
Orrenius S, Zhivotovsky B, Nicotera P. Regulation of cell death: the calcium-apoptosis link. Nat Rev Mol Cell Biol. 2003;4(7):552–65.CrossRefPubMed
16.
17.
Looi CY, Arya A, Cheah FK, Muharram B, Leong KH, Mohamad K, Wong WF, Rai N, Mustafa MR. Induction of apoptosis in human breast cancer cells via caspase pathway by vernodalin isolated from Centratherum anthelminticum (L.) Seeds. PLoS ONE. 2013;8(2):e56643.CrossRefPubMedPubMedCentral
18.
Zoli W, Ulivi P, Tesei A, Fabbri F, Rosetti M, Maltoni R, Giunchi DC, Ricotti L, Brigliadori G, Vannini I, et al. Addition of 5-fluorouracil to doxorubicin-paclitaxel sequence increases caspase-dependent apoptosis in breast cancer cell lines. Breast Cancer Res. 2005;7(5):R681–9.CrossRefPubMedPubMedCentral
19.
20.
Post JM, Hume JR, Archer SL, Weir EK. Direct role for potassium channel inhibition in hypoxic pulmonary vasoconstriction. Am J Physiol. 1992;262(4 Pt 1):C882–90.PubMed
21.
Porter AG, Janicke RU. Emerging roles of caspase-3 in apoptosis. Cell Death Differ. 1999;6(2):99–104.CrossRefPubMed
22.
Chernet BT, Levin M. Transmembrane voltage potential is an essential cellular parameter for the detection and control of tumor development in a Xenopus model. Dis Model Mech. 2013;6(3):595–607.CrossRefPubMedPubMedCentral
23.
24.
Monteith GR, McAndrew D, Faddy HM, Roberts-Thomson SJ. Calcium and cancer: targeting Ca2+ transport. Nat Rev Cancer. 2007;7(7):519–30.CrossRefPubMed
25.
Chou CC, Wu YC, Wang YF, Chou MJ, Kuo SJ, Chen DR. Capsaicin-induced apoptosis in human breast cancer MCF-7 cells through caspase-independent pathway. Oncol Rep. 2009;21(3):665–71.PubMed
26.
Sareen D, Darjatmoko SR, Albert DM, Polans AS. Mitochondria, calcium, and calpain are key mediators of resveratrol-induced apoptosis in breast cancer. Mol Pharmacol. 2007;72(6):1466–75.CrossRefPubMed
27.
Kim E-A, Jang J-H, Lee Y-H, Sung E-G, Song I-H, Kim J-Y, Kim S, Sohn H-Y, Lee T-J. Dioscin induces caspase-independent apoptosis through activation of apoptosis-inducing factor in breast cancer cells. Apoptosis. 2014;19(7):1165–75.CrossRefPubMed
28.
29.
Zhou Y, Wong CO, Cho KJ, van der Hoeven D, Liang H, Thakur DP, Luo J, Babic M, Zinsmaier KE, Zhu MX, et al. SIGNAL TRANSDUCTION. Membrane potential modulates plasma membrane phospholipid dynamics and K-Ras signaling. Science. 2015;349(6250):873–6.CrossRefPubMedPubMedCentral
Metadata
Title
Altering bioelectricity on inhibition of human breast cancer cells
Authors
Seher Berzingi
Mackenzie Newman
Han-Gang Yu
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2016
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-016-0348-8

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