期刊
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
卷 47, 期 9, 页码 3708-3716出版社
ASSOC RESEARCH VISION OPHTHALMOLOGY INC
DOI: 10.1167/iovs.06-0119
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资金
- NCI NIH HHS [R01 CA103653] Funding Source: Medline
- NIGMS NIH HHS [T32 GM07215-30] Funding Source: Medline
PURPOSE. To determine the molecular mechanisms by which resveratrol induces retinoblastoma tumor cell death. METHODS. After resveratrol treatment, Y79 tumor cell viability was measured using a fluorescence-based assay, and proapoptotic and antiproliferative effects were characterized by Hoechst stain and flow cytometry, respectively. Mitochondrial transmembrane potential ( Delta Psi(m)) was measured as a function of drug treatment using 5,5', 6,6'-tetrachloro-1,1', 3,3'-tetraethyl-benzamidazolocarbocyanin iodide ( JC-1), whereas the release of cytochrome c from mitochondria was assayed by immunoblotting and caspase activities were determined by monitoring the cleavage of fluorogenic peptide substrates. RESULTS. Resveratrol induced a dose- and time-dependent decrease in Y79 tumor cell viability and inhibited proliferation by inducing S-phase growth arrest and apoptotic cell death. Preceding cell death, resveratrol evoked a rapid dissipation of Delta Psi(m). This was followed by the release of cytochrome c into the cytoplasm and a substantial increase in the activities of caspase-9 and caspase-3. Additionally, in a cell-free system, resveratrol directly induced the depolarization of isolated mitochondria. CONCLUSIONS. These results demonstrate that resveratrol, a nontoxic natural plant compound, inhibits Y79 cell proliferation and stimulates apoptosis through activation of the mitochondrial ( intrinsic) apoptotic pathway and may warrant further exploration as an adjuvant to conventional anticancer therapies for retinoblastoma.
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