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Titolo:
Mechanism of growth inhibitory effect of mitomycin-C on cultured human retinal pigment epithelial cells: Apoptosis and cell cycle arrest
Autore:
Kang, SG; Chung, H; Yoo, YD; Lee, JG; Choi, YI; Yu, YS;
Indirizzi:
Seoul Natl Univ, Coll Med, Dept Ophthalmol, Seoul 110744, South Korea Seoul Natl Univ Seoul South Korea 110744 lmol, Seoul 110744, South Korea Eulji Univ, Sch Med, Dept Ophthalmol, Seoul, South Korea Eulji Univ Seoul South Korea h Med, Dept Ophthalmol, Seoul, South Korea Korean Canc Ctr Hosp, Lab Expt Therapeut, Seoul, South Korea Korean Canc Ctr Hosp Seoul South Korea pt Therapeut, Seoul, South Korea Inje Univ, Seoul Paik Hosp, Coll Med, Dept Ophthalmol, Seoul, South Korea Inje Univ Seoul South Korea ll Med, Dept Ophthalmol, Seoul, South Korea
Titolo Testata:
CURRENT EYE RESEARCH
fascicolo: 3, volume: 22, anno: 2001,
pagine: 174 - 181
SICI:
0271-3683(200103)22:3<174:MOGIEO>2.0.ZU;2-2
Fonte:
ISI
Lingua:
ENG
Soggetto:
PROLIFERATIVE VITREORETINOPATHY; PRIMARY TRABECULECTOMY; ADJUNCTIVE MITOMYCIN; LONG-TERM; FLUOROURACIL; VITRECTOMY; GLAUCOMA; HYPOTONY; SILICONE; AGENTS;
Keywords:
proliferative vitreoretinopathy; mitomycin-C; cell cycle arrest; apoptosis; retinal pigment epithelial cells;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
35
Recensione:
Indirizzi per estratti:
Indirizzo: Chung, H Seoul Natl Univ, Coll Med, Dept Ophthalmol, 110-744,28 Yoongondong, Seoul 110744, South Korea Seoul Natl Univ 110-744,28 Yoongondong Seoul South Korea 110744
Citazione:
S.G. Kang et al., "Mechanism of growth inhibitory effect of mitomycin-C on cultured human retinal pigment epithelial cells: Apoptosis and cell cycle arrest", CURR EYE R, 22(3), 2001, pp. 174-181

Abstract

Purpose. To investigate the therapeutic potential of Mitomycin-C (MMC) in the management of proliferative vitreoretinopathy, the antiproliferative effect of MMC on cultured human retinal pigment epithelial (RPE) cells were investigated in vitro. Methods. Drug sensitivities of cultured human RPE cells to MMC were determined using the tetrazolium dye assay. In order to detect the presence of apoptosis, DNA fragmentation was assessed by DAPI staining, and TdT-dUTP nick-end labeling (TUNEL) assay. The relative amount of DNA fragmentation was quantified by flow cytometric analysis. To analyze the cell cycle response of RPE cells to MMC, flow cytometric analysis of propidium iodide stained nuclei was performed. The levels of proteins related to DNA damage in the RPEcells were then determined by Western blot analysis. Results. MMC inhibited cell proliferation in a dose-dependent manner. The majority of RPE cells following treatment with 10 mug/ml of MMC exhibited fragmented nuclei as observed by DAPI staining and TUNEL assay. Cell cycle analysis demonstrated an accumulation of cells arrested in S and G2/M phase following treatment with 1 mug/ml of MMC. At 10 mug/ml of MMC, a dramatic increase of the cell population in the sub G1 peak, which can be considered a marker of cell death by apoptosis, was observed by flow cytometry. Western blot analysis of p53 and p21 revealed a gradual increase in the level of these proteins when RPE cells were exposed to increasing concentrations of MMC. Conclusions. This study demonstrated that the response of RPE cells to MMCwas bi-directional: 1) partial arrest of the cell cycle at S, G2/M phase, and 2) induction of apoptotic cell death.

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Documento generato il 21/09/20 alle ore 15:14:19