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D.D. Chism, N.A. Laurie, M.W. Wilson, M.A. Dyer; N–(4–hydroxylphenyl)retinamide Induces Apoptosis In Retinoblastoma Cell Lines . Invest. Ophthalmol. Vis. Sci. 2006;47(13):2817.
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Effective chemotherapies with minimal acute and delayed toxicities are needed for the treatment of retinoblastoma. N–(4–hydroxylphenyl)retinamide, (4–HPR or fenretinide), a synthetic derivative of all–trans–retinoic acid (ATRA) has been found to induce apoptosis in ATRA–resistant cell lines. The objective of this study was to examine its effects in Y79 and Weri1 retinoblastoma cell lines.
Human retinoblastoma cell lines (Weri1 and Y79) were treated with varying concentrations of 4HPR (1nM–100 µM) in vitro. We utilized flow cytometry assays to determine the effect of 4HPR on cell viability, proliferation, apoptosis, and cell cycle arrest.
Cells treated with 4–HPR showed a dose–and time–dependent induction of apoptosis. The LC50 for 4–HPR in Y79 and Weri1 cells were 3.2 µM and 6.1 µM respectively. Cell cycle studies demonstrated an S phase accumulation when cells were exposed to high concentrations of 4–HPR (> LC50 ) compared to the ethanol–treated control. A sub–G1 fraction consistent with apoptosis was also detected.
The ability of 4–HPR to induce apoptosis in retinoblastoma cell lines suggests that it could be a promising therapeutic treatment for this disease.
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