Role of apoptosis in the cytotoxic effect mediated by daunorubicin in cultured human retinal pigment epithelial cells.
To investigate whether apoptosis is involved in the therapeutic effect of daunorubicin on proliferative vitreoretinopathy (PVR), cultured human retinal pigment epithelial cells (RPE) were exposed to a cytotoxic dose of 180 microg/l daunorubicin. After 12-hour treatment with the drug and 24-hour prolonged post-incubation in the drug-free medium, progressive condensation, shrinkage of cytoplasm and nucleus, and fragmented nuclei were identified by light and electron microscopy. TUNEL assay showed the characteristic apoptotic patterns of circumscribed clumps and sometimes even dark masses in nuclei. The expression of bax protein was enhanced, and the integral optical density values for immunocytochemical expression of bax protein increased by 22.0% in the drug-treated group (P < 0.05). The results demonstrated the pivotal role of apoptotic mechanism in the cytotoxic effect mediated by daunorubicin, and confirmed the relationship between the drug-induced apoptosis and overexpression of bax protein. It suggested that the upregulation of bax mediated by daunorubicin could lead to the onset of apoptosis, and therefore contribute to its therapeutic mechanisms for the treatment of PVR.
Wang
Yu-Sheng
YS
Department of Ophthalmology, Xijing Hospital, Fourth Military Medical University, Xi'an, People's Republic of China. wangys@gmx.net
Hui
Yan-Nian
YN
Wiedemann
Peter
P
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis; D002478:Cells, Cultured; D053938:DNA Fragmentation; D003630:Daunorubicin / Q000494:pharmacology*; D006801:Humans; D008854:Microscopy, Electron; D010857:Pigment Epithelium of Eye / Q000166:cytology / Q000187:drug effects* / Q000648:ultrastructure; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051028:bcl-2-Associated X Protein
D000903:Antibiotics, Antineoplastic; C494826:BAX protein, human; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D003630:Daunorubicin