Article Data

  • Views 1489
  • Dowloads 120

Original Research

Open Access

Cl-channel blockers inhibit cell proliferation and arrest the cell cycle of human ovarian cancer cells

  • M. Li1
  • B. Wang1,*,
  • W. Lin1

1Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, China

DOI: 10.12892/ejgo200803267 Vol.29,Issue 3,May 2008 pp.267-271

Published: 10 May 2008

*Corresponding Author(s): B. Wang E-mail: wangboshandong@yahoo.com.cn

Abstract

Objective: To investigate the role of chloride channels in cell proliferation and cell cycles of human ovarian cancer cell line A2780. Methods: Chloride channel blockers were used to observe the effects of chloride channels on A2780 cells with MTT assay and flow cytometry. Results: NPPB (100 mu M) significantly inhibited the cell proliferation and affected the cell cycle, which increased the percentage of cells in the G1 phase, and reduced it in the S phase. NFA (100 mu M) and TAM (30 mu M) had similar inhibitory effects. Glibenclamide (100 mu M), however, bad no effect on cell proliferation or cycle. Moreover, chloride channel blockers Could inhibit Ca2+ influx in these cells. Conclusion: Chloride channels, voltage-gated chloride channels, and volume-sensitive chloride channels especially, play an important role in the cell proliferation and cycle of A2780 cells. It is likely that the influence of chloride channels on cell proliferation and cell cycle is mediated by a Ca2+-dependent mechanism.

Keywords

Chloride channels; Cell proliferation; Cell cycle; Ovarian cancer

Cite and Share

M. Li,B. Wang,W. Lin. Cl-channel blockers inhibit cell proliferation and arrest the cell cycle of human ovarian cancer cells. European Journal of Gynaecological Oncology. 2008. 29(3);267-271.

References

[1] O'Grady S.M., Jiang X., Ingbar D.H.: “Cl-channel activation is necessary for stimulation of Na transport in adult alveolar epithelial cells”. Am. J. Physiol. Lung Cell. Mol. Physiol., 2000, 278, L239.

[2] Nilius B., Eggermont J., Voets T., Buyse G., Manolopoulos V., Droogmans G.: “Properties of volume-regulated anion channels in mammalian cells”. Prog. Biophys. Mol. Biol., 1997, 68, 69.

[3] Valverde M.A.: “ClC channels: leaving the dark ages on the verge of a new millennium”. Curr. Opin. Cell. Biol., 1999, 11, 509.

[4] Li X., Wang T., Zhao Z., Weinman S.A.: “The CLC-3 chloride channel promotes acidification of lysosomes in CHO-K1 and Huh-7 cells”. Am. J. Physiol. Cell. Physiol., 2002, 282, C1483.

[5] Voets T., Szücs G., Droogmans G., Nilius B.: “Blockers of volume-activated Cl-currents inhibit endothelial cell proliferation”. Pflugers Arch., 1995, 431, 132.

[6] Wondergem R., Gong W., Monen S.H., Dooley S.N., Gonce J.L., Conner T.D. et al.: “Blocking swelling-activated chloride current inhibits mouse liver cell proliferation”. J. Physiol., 2001, 532, 661.

[7] Nilius B.: “Chloride channels go cell cycling”. J. Physiol., 2001, 532, 581.

[8] Chen L., Wang L., Zhu L., Nie S., Zhang J., Zhong P. et al.: “Cell cycle-dependent expression of volume-activated chloride currents in nasopharyngeal carcinoma cells”. Am. J. Physiol. Cell. Physiol., 2002, 283, C1313.

[9] Jiang B., Hattori N., Liu B., Nakayama Y., Kitagawa K., Inagaki C.: “Suppression of cell proliferation with induction of p21 by Cl (-) channel blockers in human leukemic cells”. Eur. J. Pharmacol., 2004, 488, 27.

[10] Chen L.X., Zhu L.Y., Jacob T.J., Wang L.W.: “Roles of volumeactivated Cl-currents and regulatory volume decrease in the cell cycle and proliferation in nasopharyngeal carcinoma cells”. Cell. Prolif., 2007, 40, 253.

[11] Shen M.R., Droogmans G., Eggermont J., Voets T., Ellory J.C., Nilius B.: “Differential expression of volume-regulated anion channels during cell cycle progression of human cervical cancer cells”. J. Physiol., 2000, 529, 385.

[12] Ferlini C., Scambia G., Marone M., Distefano M., Gaggini C., Ferrandina G. et al.: “Tamoxifen induces oxidative stress and apoptosis in oestrogen receptor-negative human cancer cell lines”. Br. J. Cancer, 1999, 79, 257.

[13] Suzuki M., Morita T., Iwamoto T.: “Diversity of Cl (-) channels”. Cell. Mol. Life Sci, 2006, 63, 12.

[14] Duffy S.M., Lawley W.J., Kaur D., Yang W., Bradding P.: “Inhibition of human mast cell proliferation and survival by tamoxifen in association with ion channel modulation”. J. Allergy Clin. Immunol., 2003, 112, 965.

[15] Bösl M.R., Stein V., Hübner C., Zdebik A.A., Jordt S.E., Mukhopadhyay A.K. et al.: “Male germ cells and photoreceptors, both dependent on close cell-cell interactions, degenerate upon ClC-2 Cl (-) channel disruption”. EMBO J., 2001, 20, 1289.

[16] Zheng Y.J., Furukawa T., Tajimi K., Inagaki N.: “Cl-channel blockers inhibit transition of quiescent (G0) fibroblasts into the cell cycle”. J. Cell. Physiol., 2003, 194, 376.

[17] Pappas C.A., Ullrich N., Sontheimer H.: “Reduction of glial proliferation by K+ channel blockers is mediated by changes in pHi”. Neuroreport, 1994, 6, 193.

[18] Hara-Chikuma M., Yang B., Sonawane N.D., Sasaki S., Uchida S., Verkman A.S.: “ClC-3 chloride channels facilitate endosomal acidification and chloride accumulation”. J. Biol. Chem., 2005, 280, 1241.

[19] Santella L.: “The role of calcium in the cell cycle: facts and hypotheses”. Biochem. Biophys Res. Commun., 1998, 244, 317.

[20] Parmer T.G., Ward M.D., Hait W.N.: “Effects of rottlerin, an inhibitor of calmodulin-dependent protein kinase III, on cellular proliferation, viability, and cell cycle distribution in malignant glioma cells”. Cell. Growth Differ., 1997, 8, 327.

[21] Parmer T.G., Ward M.D., Yurkow E.J., Vyas V.H., Kearney T.J., Hait W.N.: “Activity and regulation by growth factors of calmodulin-dependent protein kinase III (elongation factor 2-kinase) in human breast cancer”. Br. J. Cancer, 1999, 79, 59.

Submission Turnaround Time

Top