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NPC-14686 (Fmoc-l-homophenylalanine)-induced CaCa2+ increases and death in human prostate cancer cells.

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.
AuthorsJong-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
JournalLife sciences (Life Sci) Vol. 78 Issue 9 Pg. 964-9 (Jan 25 2006) ISSN: 0024-3205 [Print] Netherlands
PMID16188277 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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
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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