Effect of nortriptyline on cytosolic Ca2+ regulation and viability in PC3 human prostate cancer cells

Chih Chuan Pan, Chen Fu Shaw, Jong Khing Huang, Chun Chi Kuo, Daih Huang Kuo, Pochuen Shieh, Ti Lu, Wei Chuan Chen, Chin Man Ho, Chung Ren Jan*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

8 Scopus citations


The effect of nortriptyline, a tricyclic antidepressant, on Ca2+ regulation and viability in human prostate cancer cells (PC3) is unclear. The present study examined whether nortriptyline altered basal [Ca 2+]i levels in suspended PC3 cells using fura-2 as a Ca2+-sensitive fluorescent probe. Nortriptyline (50-500μM) increased [Ca2+]i in a concentration-dependent fashion. The Ca2+ signal was partially reduced by removing extracellular Ca2+, indicating that Ca2+ entry and release both contributed to the [Ca2+]i rise. Nortriptyline induced Mn2+ influx, leading to quench of fura-2 fluorescence, suggesting Ca2+ influx. This Ca2+ influx was inhibited by activation of protein kinase C, but not by inhibition of L-type Ca2+ channels. In Ca2+-free medium, pretreatment with the endoplasmic reticulum Ca2+ pump inhibitor, thapsigargin nearly abolished nortriptyline-induced Ca2+ release. Conversely, pretreatment with nortriptyline greatly reduced the inhibitor-induced [Ca2+] i rise, suggesting that nortriptyline released Ca2+ from the endoplasmic reticulum. Inhibition of phospholipase C did not change the nortriptyline-induced [Ca2+]i rise. Nortriptyline at a concentration of 10 μM increased viability in a Ca2+-independent manner. At 50 μM, nortriptyline killed 45% of cells. Nortriptyline at 10 μM did not induce apoptosis, but at 50 μM induced significant apoptosis measured by propidium iodide staining. Together, in PC3 cells, nortriptyline induced [Ca2+]i rises by causing the phospholipase C-independent Ca2+ release from the endoplasmic reticulum and Ca 2+ influx via the protein kinase C-sensitive pathway. Nortriptyline also induced both cell proliferation and death in a concentration-dependent manner. Apoptosis was involved in the cell death.

Original languageEnglish
Pages (from-to)323-330
Number of pages8
JournalDrug Development Research
Issue number5
StatePublished - 08 2010
Externally publishedYes


  • Apoptosis
  • Death
  • Nortriptyline
  • PC3 cells
  • Prostate cancer


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