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The roles of AIF and Endo G in the apoptotic effects of benzyl isothiocyanate on DU 145 human prostate cancer cells via the mitochondrial signaling pathway.
- Source :
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International journal of oncology [Int J Oncol] 2011 Mar; Vol. 38 (3), pp. 787-96. Date of Electronic Publication: 2010 Dec 30. - Publication Year :
- 2011
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Abstract
- It is well known that the response of cancer cells to chemotherapeutic drugs involves the activation of apoptotic pathways. Benzyl isothiocyanate (BITC) is an important compound found in plant food and has been shown to have anti-cancer effects on human cancer cells, but its effect on prostate cancer cells in vitro remains unknown. The aim of the present study was to investigate the effects of BITC on DU 145 human prostate cancer cells in order to clarify whether a time/concentration range for optimal BITC-induced apoptosis exists and to find the associated signaling pathway. Cell morphological changes, percentage of cell viability, DNA damage and apoptosis in DU 145 cells were examined by phase-contrast microscopy, flow cytometric assay, 4',6-diamidine-20-phenylindole dihydrochloride staining, comet assay and Western blotting analysis. The results indicate that BITC induces cell morphological changes, decreases the percentage of viable cells (induction of cell cytotoxicity), and induces DNA damage and apoptosis in DU 145 cells in a time- and dose-dependent manner. Flow cytometric assays indicated that BITC promoted reactive oxygen species and Ca2+ productions and decreased the levels of mitochondrial membrane potential (ΤYm), while the pre-treatment with N-acetylcysteine caused an increase in the percentage of viable cells. BITC also promoted caspase-3, -8 and -9 activities. Furthermore, when cells were pre-treated with the caspase-3 inhibitor and then treated with BITC, this led to an increase in the percentage of viable cells. Confocal laser microscopy examination indicated that BITC promoted the expression of AIF and Endo G, which were released from the mitochondria in DU 145 cells. In conclusion, BITC induces apoptosis in DU 145 cells through the release of AIF and Endo G from the mitochondria and also promotes caspase-3 activation.
- Subjects :
- Acetylcysteine pharmacology
Adenocarcinoma genetics
Adenocarcinoma metabolism
Antineoplastic Agents pharmacology
Apoptosis genetics
Apoptosis Inducing Factor genetics
Apoptosis Inducing Factor metabolism
Caspases metabolism
Cell Line, Tumor
Dose-Response Relationship, Drug
Drug Evaluation, Preclinical
Endodeoxyribonucleases genetics
Endodeoxyribonucleases metabolism
Gene Expression Regulation, Neoplastic drug effects
Gene Expression Regulation, Neoplastic physiology
Humans
Male
Membrane Potential, Mitochondrial drug effects
Mitochondria genetics
Mitochondria metabolism
Models, Biological
Prostatic Neoplasms genetics
Prostatic Neoplasms metabolism
Signal Transduction drug effects
Signal Transduction genetics
Signal Transduction physiology
Adenocarcinoma pathology
Apoptosis drug effects
Apoptosis Inducing Factor physiology
Endodeoxyribonucleases physiology
Isothiocyanates pharmacology
Mitochondria drug effects
Prostatic Neoplasms pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1791-2423
- Volume :
- 38
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- International journal of oncology
- Publication Type :
- Academic Journal
- Accession number :
- 21206973
- Full Text :
- https://doi.org/10.3892/ijo.2010.894