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Rocaglaol induces apoptosis and cell cycle arrest in LNCaP cells.
- Source :
-
Anticancer research [Anticancer Res] 2006 Mar-Apr; Vol. 26 (2A), pp. 947-52. - Publication Year :
- 2006
-
Abstract
- Rocaglaol is a cytotoxic cyclopenta[b]benzofuran isolated from the bark of Aglaia crassinervia. It exhibited in vitro cytotoxic activity against Lu1, LNCaP and MCF-7 cells with ED50 values of 13.8, 23.0 and 9.2 nM, respectively. DAPI staining indicated that LNCaP cells treated with rocaglaol underwent apoptosis. In order to determine whether rocaglaol-induced apoptosis is mediated by the mitochondrial pathway, apoptosis-related mitochondrial-associated proteins were studied. Rocaglaol treatment induced Bax expression through 12 to 72 h of exposure, while Bcl-xl expression was slightly decreased through 48 h, and decreased more significantly by 72 h. Cleaved caspase-9 expression was detected at 72 h, and cleaved caspase-7 was increased through 48 to 72 h. Consequently, the large fragment (89 kDa) of PARP resulting from caspase cleavage was detected at 12, 24 and 48 h, and especially at 72 h. Cleaved PARP expression was also detected at 72 h. Since rocaglaol caused dose-dependent G2/M phase arrest of LNCaP cells as indicated by flow cytometric analysis, the protein levels of cell cycle-related genes were measured. Rocaglaol treatment (230 nM) did not change cyclin B after 24- to 60-h treatment. The expression of cdc2 was not changed and phospho-cdc2 (Tyr 15) increased after 36-, 48- and 60-h treatment. In addition, protein phosphatase Cdc25C, which functions as a mitotic activator by dephosphorylation of Cdc2, decreased in a time-dependent manner after rocaglaol treatment. Taken together, these results suggest that rocaglaol is a potent anticancer drug that induces apoptosis of LNCaP cells through the mitochondrial pathway and its G2/M-phase cell cycle arrest is associated with the down-regulation of Cdc25C and the dephosphorylation of Cdc2.
- Subjects :
- Actins biosynthesis
Aglaia chemistry
Breast Neoplasms drug therapy
Breast Neoplasms pathology
Caspases biosynthesis
Cell Cycle drug effects
Cell Line, Tumor
Drug Screening Assays, Antitumor
Flow Cytometry
Humans
Lung Neoplasms drug therapy
Lung Neoplasms pathology
Male
Plant Bark chemistry
Poly(ADP-ribose) Polymerases biosynthesis
Prostatic Neoplasms metabolism
Prostatic Neoplasms pathology
bcl-2-Associated X Protein biosynthesis
bcl-X Protein biosynthesis
Antineoplastic Agents, Phytogenic pharmacology
Apoptosis drug effects
Benzofurans pharmacology
Prostatic Neoplasms drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 0250-7005
- Volume :
- 26
- Issue :
- 2A
- Database :
- MEDLINE
- Journal :
- Anticancer research
- Publication Type :
- Academic Journal
- Accession number :
- 16619491