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[Changes in mitochondrial function induced by dequalinium precede oxidative stress and apoptosis in the human prostate cancer cell line PC-3].
- Source :
-
Molekuliarnaia biologiia [Mol Biol (Mosk)] 2014 May-Jun; Vol. 48 (3), pp. 416-28. - Publication Year :
- 2014
-
Abstract
- Mitochondria play central roles in diverse physiological and pathological conditions associated with cell survival and death. Delocalized lipophilic cations, such as dequalinium (DQA), are accumulated in cancer cells attracted by the highly negative mitochondrial transmembrane potential of these cells. DQA showed a potent anticancer activity in cells from different malignancies. Here, we report the effect of DQA on PC-3 prostate cancer cells. Incubation with DQA at concentrations between 1.5 and 100 microM from 24 to 48 h decreases cell viability. The decrease in cell viability together with a loss of mitochondrial transmembrane potential induced an increase in reactive oxygen species production and cell death via caspase-3 dependent apoptotic pathway. QA was shown to cause moderate to strong cell death in a time and concentration dependent manner, causing a most advantageous effect at a concentration of 10 microM applied for a long 48 h time period, which might be a consequence of the kinetics of intracellular DQA accumulation in mitochondria, but also of the mechanisms of DQA-induced cell death. This data shows DQA as a promising agent against the human prostate cancer PC-3 cell line, activating the caspase-3 dependent apoptotic pathway. This fact might be beneficial for possible future applications in cancer therapy.
- Subjects :
- Apoptosis
Caspase 3 metabolism
Cell Line, Tumor
Cell Survival
Dose-Response Relationship, Drug
Humans
Male
Mitochondria drug effects
Reactive Oxygen Species metabolism
Antineoplastic Agents pharmacology
Dequalinium pharmacology
Membrane Potential, Mitochondrial
Mitochondria metabolism
Oxidative Stress
Prostatic Neoplasms metabolism
Subjects
Details
- Language :
- Russian
- ISSN :
- 0026-8984
- Volume :
- 48
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Molekuliarnaia biologiia
- Publication Type :
- Academic Journal
- Accession number :
- 25831891