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IK1 channel activity contributes to cisplatin sensitivity of human epidermoid cancer cells

Elbert L Lee1, Yuichi Hasegawa, Takahiro Shimizu

  • 1Department of Cell Physiology, National Institute for Physiological Sciences, Okazaki, Japan.

American Journal of Physiology. Cell Physiology
|March 28, 2008
PubMed

Insights

The calcium-activated potassium channel IK1 plays a role in how cancer cells respond to cisplatin chemotherapy. Blocking this channel improves cell survival and reduces apoptosis, suggesting it

Area of Science:

  • Cellular and Molecular Biology
  • Cancer Research
  • Ion Channel Physiology

Background:

  • Cisplatin is a key chemotherapy drug that induces cancer cell death (apoptosis) by damaging DNA.
  • The precise mechanisms of cisplatin-induced apoptosis are not fully understood.
  • Previous research implicated chloride channels in this process.

Purpose of the Study:

  • To investigate the potential role of cation channels in the cellular response to cisplatin.
  • To identify and characterize cation channels involved in cisplatin-sensitive epidermoid cancer cells.
  • To explore the functional significance of identified channels in cisplatin-induced apoptosis.

Main Methods:

  • Whole-cell patch-clamp electrophysiology was used to examine cation channel activity in KB-3-1 (KB) epidermoid cancer cells.
  • Hypotonic stress was applied to activate cation channels.
  • Channel identification involved assessing Ca2+ dependence, sensitivity to blockers (clotrimazole, triarylmethane-34), and dominant-negative constructs.
  • Semiquantitative RT-PCR and immunostaining were used to assess molecular expression.
  • Cell viability and caspase-3/7 activity assays were performed to evaluate apoptosis.

Main Results:

  • A Ca2+-activated, intermediate-conductance K+ (IK1) channel was identified in KB cells, activated by hypotonic stress.
  • This IK1 channel activity was significantly reduced or absent in cisplatin-resistant KCP-4 cells, with lower molecular expression.
  • IK1 channel blockers (clotrimazole, triarylmethane-34) reduced cisplatin-induced decreases in cell viability and caspase-3/7 activity.
  • An IK1 channel activator (1-ethyl-2-benzimidazolinone) enhanced cisplatin-induced apoptosis.

Conclusions:

  • The Ca2+-activated, intermediate-conductance K+ (IK1) channel is a component of the volume-regulatory machinery in KB epidermoid cancer cells.
  • IK1 channel activity is significantly reduced in cisplatin-resistant cells.
  • IK1 channel function is implicated in mediating the cellular response to cisplatin, potentially influencing cisplatin-induced apoptosis.

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