Abstract |
The effect of NPC-14686, a potential anti-inflammatory drug, on cytosolic free Ca2+ levels ([Ca2+]i) and growth in PC3 human prostate cancer cells was examined by using fura-2 as a fluorescent Ca2+ indicator and WST-1 as a fluorescent growth dye. NPC-14686 at concentrations above 10 microM increased [Ca2+]i in a concentration-dependent manner with an EC50 value of 100 microM. NPC-14686-induced Ca2+ influx was confirmed by Mn2+ quench of fura-2 fluorescence. The Ca2+ signal was also reduced by removing extracellular Ca2+. Pretreatment with 1 microM thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor) to deplete the endoplasmic reticulum Ca2+ nearly abolished 200 microM NPC-14686-induced Ca2+ release; and conversely pretreatment with NPC-14686 completely inhibited thapsigargin-induced Ca2+ release. The Ca2+ release induced by 200 microM NPC-14686 was not affected by inhibiting phospholipase C with 2 microM U73122. Overnight treatment with 1-500 microM NPC-14686 decreased cell viability in a concentration-dependent manner. These findings suggest that in human PC3 prostate cancer cells, NPC-14686 increases [Ca2+]i by evoking extracellular Ca2+ influx and releasing intracellular Ca2+ from the endoplasmic reticulum via a phospholiase C-independent manner. NPC-14686 may be cytotoxic to prostate cancer cells.
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Authors | Jong-Khing Huang, Chung-Shin Liu, Wei-Chuan Chen, Shiuh-Inn Liu, Shu-Shong Hsu, Hong-Tai Chang, Chiang-Ting Chou, Ching-Hong Hsieh, Chih-Hung Chang, Chung-Ren Jan |
Journal | Life sciences
(Life Sci)
Vol. 78
Issue 9
Pg. 964-9
(Jan 25 2006)
ISSN: 0024-3205 [Print] Netherlands |
PMID | 16188277
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- 2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium
- Aminobutyrates
- Calcium Channel Blockers
- Fluorescent Dyes
- NPC 14686
- Tetrazolium Salts
- Manganese
- Type C Phospholipases
- Calcium
- Fura-2
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Topics |
- Aminobutyrates
(pharmacology)
- Calcium
(metabolism)
- Calcium Channel Blockers
(pharmacology)
- Calcium Signaling
(drug effects)
- Cell Death
(drug effects)
- Cell Division
(drug effects)
- Cell Line, Tumor
- Fluorescent Dyes
- Fura-2
- Humans
- Male
- Manganese
(pharmacology)
- Prostatic Neoplasms
(drug therapy, metabolism, pathology)
- Tetrazolium Salts
- Type C Phospholipases
(physiology)
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