Advanced SearchSearch Tips
Cell proliferation inhibition effects of epigallocatechin-3-gallate in TREK2-channel overexpressing cell line
facebook(new window)  Pirnt(new window) E-mail(new window) Excel Download
 Title & Authors
Cell proliferation inhibition effects of epigallocatechin-3-gallate in TREK2-channel overexpressing cell line
Kim, Yangmi; Kim, Kyung-Ah;
  PDF(new window)
Two-pore domain potassium (K2P) channels are the targets of physiological stimuli, such as intracellular pH, bioactive lipids, and neurotransmitters, and they set the resting membrane potential. Some types of K2P channels play a critical role in both apoptosis and tumoriogenesis. Among the K2P channels, no antagonists of the TREK2 channel have been reported. The aim of the present study was to determine if the TREK2 channel is blocked and whether cell proliferation is influenced by flavonoids in the TREK2 overexpressing HEK293 cells (HEKT2). The electrophysiological current was recorded using single channel patch clamp techniques and cell proliferation was measured using a XTT assay. The electrophysiological results showed that the TREK2 channel activity was reduced to (n=5) and (n=5) by flavonoids, such as epigallocatechin-3-gallate (EGCG) and quercetin in HEKT2 cells, respectively. In contrast, the EGCG analogue, epicatechin (EC), had no significant inhibitory effects on the TREK2 single channel activity. In addition, cell proliferation was reduced to (n=4) by ECGG in the HEKT2 cells. From these results, EGCG and quercetin represent the first known TREK2 channel inhibitors and only EGCG reduced HEKT2 cell proliferation. This suggests that the flavonoids may work primarily by inhibiting the TREK2 channel, leading to a change in the resting membrane potential, and triggering the initiation of a change in intracellular signaling for cell proliferation. TREK2 channel may, at least in part, contribute to cell proliferation.
Epigallocatechin-3-gallate(EGCG);Flavonoid;Quercetin;TREK2;Two-pore domain potassium(K2P) channels;
 Cited by
S. Feliciangeli, F. C. Chatelain, D. Bichet, F. Lesage, "The family of K2P channels: salient structural and functional properties," J Physiol, Vol. 593, No. 12, pp. 2587-603, Jun, 2015. DOI: crossref(new window)

G. Di Carlo, N. Mascolo, A. A. Izzo, F. Capasso, “Flavonoids: old and new aspects of a class of natural therapeutic drugs,” Life Sci, Vol. 65, No. 4, pp. 337-53, Jun, 1999. DOI: crossref(new window)

K. Kelemen, C. Kiesecker, E. Zitron, A. Bauer, E. Scholz, R. Bloehs, D. Thomas, J. Greten, A. Remppis, W. Schoels, H. A. Katus, C. A. Karle, “Green tea flavonoid epigallocatechin-3-gallate (EGCG) inhibits cardiac hERG potassium channels,” Biochem Biophys Res Commun, Vol. 364, No. 3, pp. 429-35, Dec, 2007. DOI: crossref(new window)

K. A. Kim, Y. Kim, "The effect of flavonoids on the TREK-1 channel," Journal of the Korea Academia-Industrial cooperation Society, Vol. 12, No. 6, pp. 2660-2667, Jun, 2011. DOI: crossref(new window)

E. J. Kim, D. Kang, J. Han, "Baicalein and wogonin are activators of rat TREK-2 two-pore domain $K^+$ channel," Acta Physiol(Oxf), Vol. 202, No. 2, pp. 185-92, Jun, 2011. DOI: crossref(new window)

Y. Kim, C. Gnatenco, H. Bang, D. Kim, "Localization of TREK-2 $K^+$ channel domains that regulate channel kinetics and sensitivity to pressure, fatty acids and pHi," Pflugers Arch, Vol. 442, No. 6, pp. 952-60, Sep, 2001. DOI: crossref(new window)

G. Sandoz, D. Douguet, F. Chatelain, M. Lazdunski, F. Lesage, "Extracellular acidification exerts opposite actions on TREK1 and TREK2 potassium channels via a single conserved histidine residue," Proc Natl Acad Sci U S A, Vol. 106, No. 34, pp. 14628-33, Aug, 2009. DOI: crossref(new window)

P. Lory, J. Chemin, “Towards the discovery of novel T-type calcium channel blockers,” Expert Opin Ther Targets, Vol. 11, No. 5, pp. 717-22, May, 2007. DOI: crossref(new window)

N. Villalonga, J. C. Ferreres, J. M. Argiles, E. Condom, A. Felipe, “Potassium channels are a new target field in anticancer drug design,” Recent Pat Anticancer Drug Discov, Vol. 2, No. 3, pp. 212-23, Nov, 2007. DOI: crossref(new window)

H. Moha ou Maati, R. Peyronnet, C. Devader, J. Veyssiere, F. Labbal, C. Gandin, J. Mazella, C. Heurteaux, M. Borsotto, "A human TREK-1/HEK cell line: a highly efficient screening tool for drug development in neurological diseases," PLoS One, Vol. 6, No. 10, pp. e25602, Oct, 2011. DOI: crossref(new window)

J. Kwak, Y. Kim, "The effect of antipsychotics and antidepressants on the TREK2 channel," Journal of the Korea Academia-Industrial cooperation Society, Vol. 13, No. 5, pp. 2125-2132, May, 2012. DOI: crossref(new window)

O. P. Hamill, A. Marty, E. Neher, B. Sakmann, F. J. Sigworth, “Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches,” Pflugers Arch, Vol. 391, No. 2, pp. 85-100, Aug, 1981. DOI: crossref(new window)

H. Bang, Y. Kim, D. Kim, "TREK-2, a new member of the mechanosensitive tandem-pore $K^+$ channel family". J Biol Chem, Vol. 275, No. 23, pp. 17412-9, Jun, 2000. DOI: crossref(new window)

M. D. Brown, “Green tea (Camellia sinensis) extract and its possible role in the prevention of cancer,” Altern Med Rev, Vol. 4, No. 5, pp. 360-70, Oct, 1999.

S. G. Brohawn, "How ion channels sense mechanical force: insights from mechanosensitive K2P channels TRAAK, TREK1, and TREK2," Ann N Y Acad Sci, Vol. 1352, pp. 20-32, Sep, 2015. DOI: crossref(new window)

D. Maggioni, L. Biffi, G. Nicolini, W. Garavello, “Flavonoids in oral cancer prevention and therapy,” Eur J Cancer Prev, Vol. 24, No. 6, pp. 517-28, Nov, 2015. DOI: crossref(new window)

L. C. Pyle, J. C. Fulton, P. A. Sloane, K. Backer, M. Mazur, J. Prasain, S. Barnes, J. P. Clancy, S. M. Rowe, "Activation of CFTR by the Flavonoid Quercetin: Potential Use as a Biomarker of ${\delta}$F508 CFTR Rescue," Am J Respir Cell Mol Biol, Vol. 43, No. 5, pp. 607-616, Nov, 2010. DOI: crossref(new window)

S. Saponara, G. Sgaragli, F. Fusi, "Quercetin as a novel activator of L-type $Ca^{2+}$ channels in rat tail artery smooth muscle cells," Br J Pharmacol, Vol. 135, No. 7, pp. 1819-27, Apr, 2002. DOI: crossref(new window)

A. Cogolludo, G. Frazziano, A. M. Briones, L. Cobeno, L. Moreno, F. Lodi, M. Salaices, J. Tamargo, F. Perez-Vizcaino, "The dietary flavonoid quercetin activates BKCa currents in coronary arteries via production of $H_2O_2$. Role in vasodilatation," Cardiovasc Res, Vol. 73, No. 2, pp. 424-31, Jan, 2007. DOI: crossref(new window)

L. Yang, J. H. Ma, P. H. Zhang, A. R. Zou, D. N. Tu, “Quercetin activates human KV1.5 channels by a residue I502 in the S6 segment,” Clin Exp Pharmacol Physiol, Vol. 36, No. 2, pp. 154-61, Feb, 2009. DOI: crossref(new window)

Y. Kim, W. J. Kim, E. J. Cha, “Quercetin-induced Growth Inhibition in Human Bladder Cancer Cells Is Associated with an Increase in Ca-activated K Channels,” Korean J Physiol Pharmacol, Vol. 15, No. 5, pp. 279-83, Oct, 2011. DOI: 2011.15.5.279 crossref(new window)

B. H. Lee, S. M. Jeong, J. H. Lee, J. H. Kim, I. S. Yoon, S. H. Choi, S. M. Lee, C. G. Chang, H. C. Kim, Y. Han, H. D. Paik, Y. Kim, S. Y. Nah, “Quercetin inhibits the 5-hydroxytryptamine type 3 receptor-mediated ion current by interacting with pre-transmembrane domain I,” Mol Cells, Vol. 20, No. 1, pp. 69-73, Aug, 2005.

B. H. Lee, S. H. Hwang, S. H. Choi, T. J. Shin, J. Kang, S. M. Lee, S. Y. Nah, “Quercetin Inhibits alpha3beta4 Nicotinic Acetylcholine Receptor-Mediated Ion Currents Expressed in Xenopus Oocytes,” Korean J Physiol Pharmacol, Vol. 15, No. 1, pp. 17-22, Feb, 2011. DOI: 2011.15.1.17 crossref(new window)

H. Sun, X. P. Cheng, Z. You-Ye, P. Jiang, J. N. Zhou, “Quercetin subunit specifically reduces GlyR-mediated current in rat hippocampal neurons,” Neuroscience, Vol. 148, No. 2, pp. 548-59, Aug, 2007. DOI: crossref(new window)

B. H. Choi, J. S. Choi, D. S. Min, S. H. Yoon, D. J. Rhie, Y. H. Jo, M. S. Kim, S. J. Hahn, “Effects of (-)-epigallocatechin-3-gallate, the main component of green tea, on the cloned rat brain Kv1.5 potassium channels,” Biochem Pharmacol, Vol. 62, No. 5, pp. 527-35, Sep, 2001. DOI: crossref(new window)

Z. Wang, "Roles of $K^+$ channels in regulating tumour cell proliferation and apoptosis," Pflugers Arch, Vol. 448, No. 3, pp. 274-86, Jun, 2004. DOI: crossref(new window)

K. Kunzelmann, “Ion channels and cancer,” J Membr Biol, Vol. 205, No. 3, pp. 159-73, Jun, 2005. DOI: crossref(new window)

H. Ouadid-Ahidouch, A. Ahidouch, "$K^+$ channel expression in human breast cancer cells: involvement in cell cycle regulation and carcinogenesis," J Membr Biol, Vol. 221, No. 1, pp. 1-6, Jan, 2008. DOI: crossref(new window)

B. Rouzaire-Dubois, J. M. Dubois, "$K^+$ channel block-induced mammalian neuroblastoma cell swelling: a possible mechanism to influence proliferation," J Physiol, Vol. 510(Pt 1), pp. 93-102, Jul, 1998. DOI: crossref(new window)

A. Becchetti, “Ion channels and transporters in cancer. 1. Ion channels and cell proliferation in cancer,” Am J Physiol Cell Physiol, Vol. 301, No. 2, pp. C255-65, Aug, 2011. DOI: crossref(new window)

B. Rouzaire-Dubois, V. Gerard, J. M. Dubois, "Involvement of $K^+$ channels in the quercetin-induced in hibition of neuroblastoma cell growth," Pflugers Arch, Vol. 423, No. 3-4, pp. 202-5, May, 1993. DOI: crossref(new window)

J. Y. Moon, Y. W. Song, H. B. Hyun, S. K. Cho, “Chemical Composition and Antiproliferative Activity of Supercritical Extract of Immature Citrus Peel in human cervical carcinoma HeLa cells,” Journal of the Korea Academia-Industrial cooperation Society, Vol. 16, No. 12, pp. 8836-8843, Dec, 2015. crossref(new window)