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A. Gupta, K.R. Van Quill, N.A. Sharara, J.M. O'Brien; Effects of All-trans Retinoic Acid and 9-cis Retinoic Acid in Human Retinoblastoma Cell Lines . Invest. Ophthalmol. Vis. Sci. 2003;44(13):1580.
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Purpose: All-trans retinoic acid (ATRA) and 9-cis retinoic acid (9-CRA) are naturally occurring retinoids that have demonstrated significant anticancer effects in animal tumor models and in clinical trials of cancer patients. In this study we investigated the potential utility of ATRA and 9-CRA in the clinical management of retinoblastoma. Methods: Dose-dependent antiproliferative effects of ATRA and 9-CRA were investigated in human retinoblastoma cells in vitro. Two established retinoblastoma cell lines, Y79 and Weri-RB1, were treated with ATRA and 9-CRA at concentrations ranging from 0.1 to 20µM and 0.01 to 10µM, respectively. At 96 hours post-treatment, antiproliferative effects were determined by WST-1 Cell Proliferation Assay (Roche) and Cell Titer-Glo Luminescent Cell Viability Assay (Promega). Absorbance and luminescence values from the two assays were converted into live cell counts using standard curves. All assays were performed in triplicate. Results were expressed as percent viability and considered positive if the concentration required to induce 50% growth inhibition (IC50) fell within clinically achievable levels. Results: At 96 hours post-treatment, both ATRA and 9-CRA demonstrated mild antiproliferative effects that were not dose-dependent. ATRA inhibited cell growth by approximately 35% at concentrations ≥1µM in both cell lines. 9-CRA inhibited cell growth by approximately 40% at concentrations ≥0.25µM in both cell lines. However, these retinoids failed to induce an IC50, even at concentrations that well exceeded clinically achievable levels. Conclusions: Although ATRA and 9-CRA were ineffective at inhibiting retinoblastoma cell growth by 50%, these agents did demonstrate some antiproliferative effects in Y79 and Weri-RB1 cell lines at clinically achievable concentrations. Therefore, ATRA and 9-CRA could have clinical utility as adjuvants in current retinoblastoma therapy. Retinoids have the potential to increase treatment efficacy and reduce total chemotherapeutic exposure in patients with this cancer predisposition syndrome.
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