The Synergistic Cytotoxic and Apoptotic Effect of Resveratrol and Naringenin on Y79 Retinoblastoma Cell Line

Abstract

Background: Resveratrol is a phenolic natural product which is found in red grapes also in Japanese knotweed root (Polygonum cuspidatum). Naringenin is one of the flavonoid compounds found in landing grape and other citrus fruits. Both agents exert antioxidant and anti-inflammatory properties. Objective: In this study, we investigated the effect of Resveratrol and Naringenin in an in vitro model of retinoblastoma of the eye. Method: XTT and trypan blue assays used to evaluate the anti-proliferative/cytotixic effect of resveratrol and naringenin in Y79 cells. By the aid of AnnexinV/PI flow cytometry the kind of cell death investigated. To asses important gene expression level at mRNA level involve in apoptosis, Real-time PCR utilized. Results: Naringenin and resveratrol significantly decreased proliferation and stimulated cell death (mostly apoptosis) in Y79 cells at 50 and 100 (μg/ml) after 24 and 48 hours. More cytotoxic effect observed after 48 hours. Furthermore expression level of Bax and Bcl2 mRNAs altered significantly in all samples treated with 50 (μg/ml) of naringenin, resveratrol, or simultaneously with both. P21 mRNAs expression altered in all mentioned samples except those treated with 50 (μg/ml) of resveratrol. Results: Naringenin and resveratrol significantly decreased proliferation and stimulated cell death (mostly apoptosis) in Y79 cells at 50 and 100 (μg/ml) after 24 and 48 hours. More cytotoxic effect observed after 48 hours. Furthermore expression level of Bax and Bcl2 mRNAs altered significantly in all samples treated with 50 (μg/ml) of naringenin, resveratrol, or simultaneously with both. P21 mRNAs expression altered in all mentioned samples except those treated with 50 (μg/ml) of resveratrol. Conclusion: Based on the results, it can be concluded that resveratrol and naringenin can decrease cell viability in retinoblastoma cells in an in vitro dose/time-dependent manner. Albeit more studies needed to shed the light on the mechanism of action, our data reveals a potential synergistic cytotoxic effect of naringenin and resveratrol on Y79 cells in 48 hours.

The Role of Resveratrol in Eye Diseases—A Review of the Literature

“…Sareen et al demonstrated that due to RSV, the growth of the retinoblastoma cell line in a time- and dose-dependent manner is inhibited, while cycle S-phase cell arrest and apoptosis are promoted [ 106 ]. Other researchers reached similar results [ 107 ].…”

“…RSV treatment results in death and regression of neoplastic cells [ 105 , 106 , 107 ]. RSV suppresses the growth of uveal melanoma through early mitochondrial dysfunction and caspase-3 activation [ 105 ].…”