ABSTRACT
BACKGROUND: Resveratrol is a phenolic natural product, which is found in red grapes and 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, the effect of Resveratrol and Naringenin in an in vitro model of retinoblastoma of the eye has been investigated. METHODS: XTT and trypan blue assays were used to evaluate the anti-proliferative/cytotixic effect of resveratrol and naringenin in Y79 cells. With the aid of AnnexinV/PI flow cytometry, the kind of cell death was investigated. To assess important gene expression levels at mRNA level involved in apoptosis, Real-time PCR was 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. Additional cytotoxic effect was 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 are needed to shed the light on the mechanism of action, our data reveal a potential synergistic cytotoxic effect of naringenin and resveratrol on Y79 cells in 48 hours.
Subject(s)
Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Flavanones/pharmacology , Resveratrol/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Proliferation/drug effects , Cell Survival/drug effects , Drug Screening Assays, Antitumor , Flavanones/chemical synthesis , Flavanones/chemistry , Humans , Resveratrol/chemical synthesis , Resveratrol/chemistry , Tumor Cells, CulturedABSTRACT
BACKGROUND: Osteosarcoma (OS) is known as the malignant tumors in the bone. Cyanidin 3-OGlucoside (C3G) has a potential to induce the apoptotic cell death in different cancer cells; however, the mechanisms of action for C3G have not been clarified yet. OBJECTIVE: In this study, the apoptotic effects of C3G on three different osteosarcoma cell lines including Saso-2, MG-63, and G-292 (clone A141B1) were investigated. METHODOLOGY: The 24-hr IC50 of C3G for Saso-2, G-292, and MG-63 cells was evaluated by the MTT assay. Apoptosis induction in these cell lines after treatment with the C3G was approved by the Annexin V/PI flow cytometry. Changes at the mRNA expression level of PPARγ, P21, Bax, and Bcl-xl genes were investigated by real-time Polymerase Chain Reaction (PCR) technique, and P21 expression was further confirmed by the western blotting. RESULTS: The MTT assay results demonstrated that the 24-hr IC50 of C3G was equal to 110µg/ml for Saso-2 and G-292 cells while it was about 140µg/ml for the MG-63 cells. The results of real-time PCR clearly showed that treatment of the cells with 24hrs IC50 of C3G caused the upregulation of PPARγ, P21, and Bax genes. Moreover, western blot analysis confirmed that P21 protein overexpressed endogenously after treatment of the cells with the C3G, and it was more upregulated in the MG-63 cells compared to the other cell lines. CONCLUSION: According to the findings of the study, the C3G is a novel anti-osteosarcoma agent with the ability to induce the apoptosis in different osteosarcoma cells through upregulation of the PPARγ and P21 genes.
