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Review ArticleExperimental Studies

Volume-sensitive Cl- Channel as a Regulator of Acquired Cisplatin Resistance

TAKAHIRO SHIMIZU, ELBERT LAN LEE, TOMOKO ISE and YASUNOBU OKADA
Anticancer Research January 2008, 28 (1A) 75-83;
TAKAHIRO SHIMIZU
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ELBERT LAN LEE
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TOMOKO ISE
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YASUNOBU OKADA
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  • For correspondence: okada@nips.ac.jp
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Abstract

The platinum-based drug cisplatin (cis-diamminedichloroplatinum (II)) is widely used in cancer therapy. However, cancer cells can develop resistance after exposure to cisplatin. Recently, many studies have pointed to the involvement of plasma membrane ion channels in a cell's response to cisplatin. Our group has found that pretreatment with cisplatin enhanced the activity of volume-sensitive Cl-channels in human epidermoid cancer KB cells; cisplatin-resistant KCP-4 cells derived from KB cells, on the other hand, lacked functional expression of these channels. This suggests that the activity of volume-sensitive Cl- channels is an important factor in determining the sensitivity of cancer cells to cisplatin. Furthermore, when volume-sensitive Cl- channel function was partially restored in cisplatin-resistant KCP-4 cells treated with a histone deacetylase inhibitor, KCP-4 cells exhibited a restoration of sensitivity to cisplatin; this increased sensitivity was inhibited by a volume-sensitive Cl- channel blocker. We therefore propose that impaired activity of the volume-sensitive Cl- channel is involved in the acquired cisplatin resistance of these cancer cells. In this review, we will outline the relationship between volume-sensitive Cl- channels, cisplatin-induced apoptosis, and cisplatin resistance. Activating the volume-sensitive outwardly-rectifying Cl- channel may be a new strategy in treating clinical cisplatin resistance.

  • Cl- channel
  • cancer
  • cell volume
  • apoptosis
  • cisplatin
  • drug resistance
  • review
  • Received September 13, 2007.
  • Revision received November 14, 2007.
  • Accepted December 17, 2007.
  • Copyright© 2008 International Institute of Anticaner Research (Dr. John G. Delinassios), All rights reserved
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Anticancer Research: 28 (1A)
Anticancer Research
Vol. 28, Issue 1A
January-February 2008
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Volume-sensitive Cl- Channel as a Regulator of Acquired Cisplatin Resistance
TAKAHIRO SHIMIZU, ELBERT LAN LEE, TOMOKO ISE, YASUNOBU OKADA
Anticancer Research Jan 2008, 28 (1A) 75-83;

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Volume-sensitive Cl- Channel as a Regulator of Acquired Cisplatin Resistance
TAKAHIRO SHIMIZU, ELBERT LAN LEE, TOMOKO ISE, YASUNOBU OKADA
Anticancer Research Jan 2008, 28 (1A) 75-83;
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