Nordihydroguaiaretic acid-induced Ca 2+ handling and cytotoxicity in human prostate cancer cells

Jong Khing Huang, Wei Chuan Chen, Chun Jen Huang, Shu Shong Hsu, Jin Shyr Chen, He Hsiung Cheng, Hong Tai Chang, Bang Ping Jiann, Chung Ren Jan

Research output: Contribution to journalJournal Article peer-review

24 Scopus citations

Abstract

The effect of nordihydroguaiaretic acid (NDGA), a compound commonly used as a lipoxygenases inhibitor, on intracellular free Ca 2+ levels ([Ca 2+] i) in PC3 human prostate cancer cells was investigated. [Ca 2+] i was measured by using the Ca 2+-sensitive dye fura-2. NDGA increased [Ca 2+] i in a concentration-dependent manner with an EC 50 of 30 μM. The Ca 2+ signal comprised a gradual and sustained increase. Removal of extracellular Ca 2+ partly decreased the NDGA-induced [Ca 2+] i increase, suggesting that the Ca 2+ signal was due to both extracellular Ca 2+ influx and intracellular Ca 2+ release. NDGA-induced Ca 2+ influx was independently confirmed by measuring NDGA-induced Mn 2+-coupled quench of fura-2 fluorescence. The NDGA-induced Ca 2+ influx was not affected by L-type Ca 2+ channel blockers. In Ca 2+-free medium, the NDGA-induced [Ca 2+] i increase was abolished by pretreatment with 1 μM thapsigargin (an endoplasmic reticulum Ca 2+pump inhibitor), and conversely, pretreatment with NDGA abolished thapsigargin-induced [Ca 2+] i increase. NDGA-induced intracellular Ca 2+ release was not altered by inhibition of phospholipase C. Overnight treatment with 20-50 μM NDGA inhibited cell proliferation rate in a concentration-dependent manner. Several other lipoxygenases inhibitors did not alter [Ca 2+] i. Collectively, this study shows that in prostate cells, NDGA induced a [Ca 2+] i increase via releasing stored Ca 2+from the endoplasmic reticulum in a manner independent of phospholipase C activity, and by causing Ca 2+ influx. NDGA also caused cytotoxicity at higher concentrations.

Original languageEnglish
Pages (from-to)2341-2351
Number of pages11
JournalLife Sciences
Volume75
Issue number19
DOIs
StatePublished - 24 09 2004
Externally publishedYes

Keywords

  • Ca
  • Fura-2
  • PC3
  • Prostate
  • Thapsigargin

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