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Toxic effects of melphalan, topotecan and carboplatin on retinal pigment epithelial cells
Author(s) -
Süsskind Daniela,
Hagemann Ulrike,
Schrader Merle,
Januschowski Kai,
Schnichels Sven,
Aisenbrey Sabine
Publication year - 2016
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/aos.12990
Subject(s) - carboplatin , topotecan , melphalan , viability assay , apoptosis , pharmacology , cell growth , chemistry , biology , cisplatin , medicine , chemotherapy , biochemistry
Abstract Purpose Clinical evidence of retinal pigment epithelium ( RPE ) alterations after intra‐arterial ( IAC ) and intravitreal chemotherapy ( IV iC) of retinoblastoma has been reported. We, therefore, investigated the cellular toxic effects of melphalan, topotecan and carboplatin on the RPE in a cell culture model. Methods The effects of melphalan, carboplatin and topotecan on ARPE 19 cell morphology were examined by phase contrast microscopy. Cell proliferation was quantified by BrdU incorporation, cell viability studied via MTS assays, and cell densities were estimated by Crystal Violet staining, and apoptosis induction studied via caspase 3/7‐activity assays after a 24‐hr incubation period. Staurosporine, media without fetal bovine serum, diluents of melphalan, carboplatin and topotecan were applied as positive and negative controls, respectively. Results We observed a concentration‐dependent increase in the number and size of gaps in the ARPE 19 cell layer with each drug. There was a significant decrease in proliferative activity and cell viability of RPE cells as well as an increase in apoptosis after 24 hrs culture in media supplemented with melphalan and topotecan. Carboplatin had comparable effects on cell proliferation and cell viability; however, no significant apoptotic impacts were observed. The three cytostatic drugs had insignificant effects on cell density measurements. Conclusions Morphological monitoring and toxicity assays indicate a direct toxic effect of melphalan and the other two cytostatic drugs on ARPE 19 cells. Thus, a direct toxic effect of melphalan in vivo after IAC or IV iC on the RPE seems probable and may explain the clinical and angiographic RPE alterations observed in some retinoblastoma patients.