Insulin-like factor binding protein-3 promotes the G1 cell cycle arrest in several cancer cell lines |
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Authors: | Chen Wu Xiaobo Liu Yuanyuan Wang Huanna Tian Yuanyuan Xie Qinjian Li Xiaokang Zhang Fangming Liu |
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Institution: | 1. College of Life Sciences, Hebei University, Baoding, Hebei, 071002, PR China;2. College of Pharmaceutical Sciences, Hebei University, Baoding, Hebei, 071002, PR China |
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Abstract: | Insulin-like growth factor binding protein-3 (IGFBP-3) is a multi-functional protein known to induce apoptosis of various cancer cells in an insulin-like growth factor (IGF)-dependent and IGF-independent manner. In our previous study, we found that IGFBP-3 induced apoptosis through the activation of caspases in 786-O cells. In this study, we further examined that whether IGFBP-3 induced apoptosis through the induction of cell cycle arrest in 786-O, A549 and MCF-7 cells. Our results showed that overexpressed IGFBP-3 resulted in typical apoptotic ultrastructures in A549 cells under transmission electron microscope. The result of flow cytometry analysis indicated that IGFBP-3 arrested the cell cycle at G1-S phase in 786-O, A549 and MCF-7 cells. In A549 cells, quantitative real-time PCR and Western blot analysis showed a significant change in the expression of cell cycle-regulated proteins—a decrease in cyclin E1 expression, an increase in p21 expression. These results indicate a possible mechanism for G1 cell cycle arrest by IGFBP-3. Taken together, cyclin E1 and p21 may play important roles in the IGFBP-3-inducing G1 cell cycle arrest and apoptosis in several human cancer cells. |
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Keywords: | IGFBP-3 insulin-like growth factor binding protein-3 IGF insulin-like growth factor IGFBPs insulin-like growth factor binding proteins TNF-α tumor necrosis factor-α RXRα retinoid X rexeptorα CDK cyclin-dependent kinase FCS fetal calf serum TEM transmission electron microscope examination PI propidium iodide FITC fluorescein isothiocyanate FACS fluorescence-activated cell sorting qPCR quantitative PCR GAPDH glyceraldehyde 3-phosphate dehydrogenase TGF transforming growth factor APC anaphase promoting complex |
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