Apoptotic Effect of Arctigenin on Human Renal Cancer Cells by Arresting Cell Cycle and Down regulating P13k/Akt Pathway

摘要

Background and Objective: The activation of P13k/Akt pathway is a major mechanism which inhibits apoptosis and leads to human malignancies. Arctigenin, a flavonoid, has antioxidant property and induces apoptosis in variety of cancer cells. Therefore, this study investigated the growth inhibitory and apoptotic activity of arctigenin against 786-O renal cancer cell (RCC) line and their underlying signaling mechanism. Materials and Methods: Dose dependent cell viability and cytotoxicity assay of arctigenin on 786-O RCC line was performed using MTT and LDH assay, respectively. Further, arctigenin-induced cell cycle arrest and apoptotic cell death was evaluated using flow cytometry. In addition, the effect of arctigenin in regulating pro-apoptotic caspase cascade and PI3k/Akt pathway was analyzed using standard kits and Western blotting. Results: MTT and LDH assay results showed significant anti-proliferative effect of arctigenin on 786-O RCC line, dose dependently. Furthermore, flow cytometric data indicated cell cycle arrest within G2/M phase and activation of apoptosis in RCC after arctigenin treatment. The association of signaling molecules in inducing apoptosis was confirmed by the elevation of caspase-9 and caspase-3 levels that further downregulated PI3k/Akt signaling pathway, dose dependently. Conclusion: The arctigenin exerts cytotoxic activity on renal cancer cells and perform apoptotic activity by downregulating PI3k/Akt signaling pathway.