5-Iodotubercidin Inhibits the Growth of Insulinoma Cells by Inducing Apoptosis

Background/Aims: 5-Iodotubercidin, a type of purine derivative, has attracted increasingly attention in tumor chemotherapy because of its potential as an anti-tumor agent in recent years. In this study, we confirmed the effects on apoptosis in insulinoma cell lines induced by 5-iodotubercidin and try to illuminate the underlying mechanisms. Methods: we used 5-Iodotubercidin in the treatment of insulinoma cells and the cell proliferation was examined using CCK-8 assay , colony-forming assays and insulinoma animal models. Cell apoptosis was examined using TUNEL assays and western blotting. Cellular DNA damage were showed by comet assay and immunofluorescence. The expression of apoptosis-regulating proteins and DNA damage biomarker were investigated by western blotting. Subcutaneous inoculation of the insulinoma cells into nude mice to measure blood glucose, insulin levels and tumor growth. ATM siRNA and p53 siRNA were used as loss-of-function targets to evaluate 5-Iodotubercidin treatment. Results: 5-Iodotubercidin inhibited the proliferation of insulinoma cells and induced DNA damage and cell apoptosis. Moreover, 5-iodotubercidin induce ATM and p53 activited. In vivo, 5-Iodotubercidin inhibited the growth of Ins-1 and Min-6 cells xenografts in nude mice. Conclusions: 5-iodotubercidin induce DNA damage leading to insulinoma cells apoptosis by activating ATM/p53 pathway. Therefore, this is a potential strategy for treating Insulinoma.