Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on sleep in brain health

LIVE: Thursday 2nd May 2024, 18:00-19:30 (CEST)

Quality sleep is essential for health. But what happens to our brains when sleep patterns are disturbed? Join our experts to explore the interplay between sleep disruption and neurological diseases, and the questions that you need to be asking your patients to help you prevent the harmful effects of sleep deprivation.
ADVANCED SEARCH
Log in
Top
Cancer Cell International
Published in: Cancer Cell International 1/2011

Open Access 01-12-2011 | Primary research

The role of Eag and HERG channels in cell proliferation and apoptotic cell death in SK-OV-3 ovarian cancer cell line

Authors: Viren Asher, Averil Warren, Robert Shaw, Heidi Sowter, Anish Bali, Raheela Khan

Published in: Cancer Cell International | Issue 1/2011

Login to get access

Abstract

Background

The voltage gated potassium (K+) channels Eag and HERG have been implicated in the pathogenesis of various cancers, through association with cell cycle changes and programmed cell death. The role of these channels in the onset and progression of ovarian cancer is unknown. An understanding of mechanism by which Eag and HERG channels affect cell proliferation in ovarian cancer cells is required and therefore we investigated their role in cell proliferation and their effect on the cell cycle and apoptosis of ovarian cancer cells.

Methods

The presence of Eag and HERG was determined in SK-OV-3 cells using immunofluorescence and western blotting. The effect of the Eag blockers (imipramine and clofilium) and HERG blockers (E-4031 and ergtoxin) on cell proliferation was assessed using the MTS assay with further investigation of their role in the cell cycle and apoptosis determined by flow cytometry.

Results

Eag and HERG channels were present in the cytoplasm and nuclei of SK-OV-3 cells. There was significant inhibition of proliferation of SK-OV-3 cells by imipramine (P < 0.001) and ergtoxin (P < 0.05) at 72 hours of culture. Incubation of cells with ergtoxin led to the accumulation of cells in the S and G2/M phase, while cells accumulated in S phase after incubation with E-4031, with no effect on apoptosis. Imipramine did not affect the cell cycle but increased the proportion of SK-OV-3 cells undergoing early apoptosis.

Conclusion

Both Eag and HERG channels are expressed in SK-OV-3 ovarian cancer cells and have a role in cell proliferation. HERG channels affect the cell cycle while Eag channels are implicated in the inhibition of apoptosis of ovarian cancer cells. The family of Eag channels may represent a new therapeutic target for the treatment of ovarian cancer.
Appendix
Available only for authorised users
Literature
1.
Le Guennec JY, Ouadid-Ahidouch H, Soriani O, Besson P, Ahidouch A, Vandier C: Voltage-gated ion channels, new targets in anti-cancer research. Recent Pat Anticancer Drug Discov. 2007, 2: 189-202. 10.2174/157489207782497244.CrossRefPubMed
2.
Ganetzky B, Robertson GA, Wilson GF, Trudeau MC, Titus SA: The eag family of K+ channels in Drosophila and mammals. Ann N Y Acad Sci. 1999, 868: 356-369. 10.1111/j.1749-6632.1999.tb11297.x.CrossRefPubMed
3.
Pardo LA, del Camino D, Sanchez A, Alves F, Bruggemann A, Beckh S, Stuhmer W: Oncogenic potential of Eag K channels. EMBO J. 1999, 18: 5540-5547. 10.1093/emboj/18.20.5540.PubMedCentralCrossRefPubMed
4.
Camacho J: Ether a go-go potassium channels and cancer. Cancer Lett. 2006, 233: 1-9. 10.1016/j.canlet.2005.02.016.CrossRefPubMed
5.
Curran ME, Splawski I, Timothy KW, Vincent GM, Green ED, Keating MT: A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome. Cell. 1995, 80: 795-803. 10.1016/0092-8674(95)90358-5.CrossRefPubMed
6.
Crociani O, Guasti L, Balzi M, Becchetti A, Wanke E, Olivotto M, Wymore RS, Arcangeli A: Cell cycle-dependent expression of HERG1 and HERG1B isoforms in tumor cells. J Biol Chem. 2003, 278: 2947-2955. 10.1074/jbc.M210789200.CrossRefPubMed
7.
Zhanping W, Xiaoyu P, Na C, Shenglan W, Bo W: Voltage-gated K+ channels are associated with cell proliferation and cell cycle of ovarian cancer cell. Gynecol Oncol. 2007, 104: 455-460. 10.1016/j.ygyno.2006.08.033.CrossRefPubMed
8.
9.
Garcia-Ferreiro RE, Kerschensteiner D, Major F, Monje F, Stuhmer W, Pardo LA: Mechanism of block of hEag1 K+ channels by imipramine and astemizole. J Gen Physiol. 2004, 124: 301-317. 10.1085/jgp.200409041.PubMedCentralCrossRefPubMed
10.
Gessner G, Heinemann SH: Inhibition of hEAG1 and hERG1 potassium channels by clofilium and its tertiary analogue LY97241. Br J Pharmacol. 2003, 138: 161-171. 10.1038/sj.bjp.0705025.PubMedCentralCrossRefPubMed
11.
Roy J, Vantol B, Cowley EA, Blay J, Linsdell P: Pharmacological separation of hEAG and hERG K+ channel function in the human mammary carcinoma cell line MCF-7. Oncol Rep. 2008, 19: 1511-1516.PubMed
12.
Pardo-Lopez L, Garcia-Valdes J, Gurrola GB, Robertson GA, Possani LD: Mapping the receptor site for ergtoxin, a specific blocker of ERG channels. FEBS Lett. 2002, 510: 45-49. 10.1016/S0014-5793(01)03218-5.CrossRefPubMed
13.
Gurrola GB, Rosati B, Rocchetti M, Pimienta G, Zaza A, Arcangeli A, Olivotto M, Possani LD, Wanke E: A toxin to nervous, cardiac, and endocrine ERG K+ channels isolated from Centruroides noxius scorpion venom. FASEB J. 1999, 13: 953-962.PubMed
14.
Zhang G, Gurtu V, Kain SR, Yan G: Early detection of apoptosis using a fluorescent conjugate of annexin V. Biotechniques. 1997, 23: 525-531.PubMed
15.
Pardo LA, Suhmer W: Eag1 as a cancer target. Expert Opin Ther Targets. 2008, 12: 837-843. 10.1517/14728222.12.7.837.CrossRefPubMed
16.
Trudeau MC, Titus SA, Branchaw JL, Ganetzky B, Robertson GA: Functional analysis of a mouse brain Elk-type K+ channel. J Neurosci. 1999, 19: 2906-2918.PubMed
17.
Li H, Liu L, Guo L, Zhang J, Du W, Li X, Liu W, Chen X, Huang S: HERG K+ channel expression in CD34+/CD38-/CD123(high) cells and primary leukemia cells and analysis of its regulation in leukemia cells. Int J Hematol. 2008, 87: 387-392. 10.1007/s12185-008-0056-9.CrossRefPubMed
18.
Dolderer JH, Schuldes H, Bockhorn H, Altmannsberger M, Lambers C, von Zabern D, Jonas D, Schwegler H, Linke R, Schroder UH: HERG1 gene expression as a specific tumor marker in colorectal tissues. Eur J Surg Oncol. 36: 72-77.
19.
Pardo LA, Contreras-Jurado C, Zientkowska M, Alves F, Stuhmer W: Role of voltage-gated potassium channels in cancer. J Membr Biol. 2005, 205: 115-124. 10.1007/s00232-005-0776-1.CrossRefPubMed
20.
Gavrilova-Ruch O, Schonherr K, Gessner G, Schonherr R, Klapperstuck T, Wohlrab W, Heinemann SH: Effects of imipramine on ion channels and proliferation of IGR1 melanoma cells. J Membr Biol. 2002, 188: 137-149. 10.1007/s00232-001-0181-3.CrossRefPubMed
21.
Levkovitz Y, Gil-Ad I, Zeldich E, Dayag M, Weizman A: Differential induction of apoptosis by antidepressants in glioma and neuroblastoma cell lines: evidence for p-c-Jun, cytochrome c, and caspase-3 involvement. J Mol Neurosci. 2005, 27: 29-42. 10.1385/JMN:27:1:029.CrossRefPubMed
22.
Choi BY, Kim HY, Lee KH, Cho YH, Kong G: Clofilium, a potassium channel blocker, induces apoptosis of human promyelocytic leukemia (HL-60) cells via Bcl-2-insensitive activation of caspase-3. Cancer Lett. 1999, 147: 85-93. 10.1016/S0304-3835(99)00280-3.CrossRefPubMed
23.
Metadata
Title
The role of Eag and HERG channels in cell proliferation and apoptotic cell death in SK-OV-3 ovarian cancer cell line
Authors
Viren Asher
Averil Warren
Robert Shaw
Heidi Sowter
Anish Bali
Raheela Khan
Publication date
01-12-2011
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2011
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/1475-2867-11-6

Other articles of this Issue 1/2011

Cancer Cell International 1/2011 Go to the issue

Primary research

In vitro activities of novel 4-HPR derivatives on a panel of rhabdoid and other tumor cell lines

Primary research

In vitro effects of 2-methoxyestradiol-bis-sulphamate on reactive oxygen species and possible apoptosis induction in a breast adenocarcinoma cell line

Primary research

Potassium bicarbonate and D-ribose effects on A72 canine and HTB-126 human cancer cell line proliferation in vitro

Primary research

Effect of Benzothiazole based conjugates in causing apoptosis by Regulating p53, PTEN and MAP Kinase proteins affecting miR-195a and miR-101-1

Primary research

Vitamin K3 and vitamin C alone or in combination induced apoptosis in leukemia cells by a similar oxidative stress signalling mechanism

Review

Translesion DNA synthesis in the context of cancer research
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits