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Effects of timolol on Ca2+ handling and viability in human prostate cancer cells

Jue-Long Wang1, Chiang-Ting Chou2, Wei-Zhe Liang3,4,5

  • 1a Department of Rehabilitation, Kaohsiung Veterans General Hospital , Kaohsiung , Taiwan.

Toxicology Mechanisms and Methods
|November 6, 2018
PubMed

Insights

Timolol, a glaucoma drug, increases intracellular calcium and causes cell death in prostate cancer cells by affecting calcium release and entry pathways. This cell death mechanism is independent of the initial calcium rise.

Area of Science:

  • Oncology
  • Cell Physiology
  • Pharmacology

Background:

  • Timolol is widely used for glaucoma treatment.
  • Timolol's effects on calcium (Ca2+) signaling are known in various cell types.
  • Its impact on Ca2+ homeostasis and viability in prostate cancer cells remains unexplored.

Purpose of the Study:

  • To investigate the effect of timolol on intracellular Ca2+ concentrations ([Ca2+]i) and cell viability in PC3 human prostate cancer cells.
  • To elucidate the mechanisms of timolol-induced Ca2+ changes and cell death.

Main Methods:

  • PC3 cells were treated with varying concentrations of timolol.
  • Intracellular Ca2+ levels were measured using calcium indicators.
  • Mechanisms of Ca2+ handling were assessed using specific inhibitors and activators of ion channels, pumps, and signaling pathways.
  • Cell viability was determined using cell counting and cytotoxicity assays.

Main Results:

  • Timolol induced dose-dependent increases in [Ca2+]i in PC3 cells.
  • This rise involved Ca2+ release from the endoplasmic reticulum via phospholipase C (PLC) and Ca2+ influx through store-operated Ca2+ channels regulated by protein kinase C (PKC).
  • Timolol also induced cell death, which was not reversed by chelating intracellular Ca2+.

Conclusions:

  • Timolol modulates Ca2+ homeostasis in PC3 cells through PLC-dependent Ca2+ release and PKC-regulated store-operated Ca2+ entry.
  • Timolol exhibits cytotoxic effects on PC3 cells, independent of the observed intracellular Ca2+ fluctuations.
  • These findings suggest potential therapeutic avenues for timolol in prostate cancer treatment.
Keywords:
Caendoplasmic reticulumhuman prostate cancer cellstimololviability

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