Insulin-like factor binding protein-3 promotes the G1 cell cycle arrest in several cancer cell lines

• Published in: Gene 2013-01, Vol.512 (1), p.127-133
• Main Authors: Wu, Chen, Liu, Xiaobo, Wang, Yuanyuan, Tian, Huanna, Xie, Yuanyuan, Li, Qinjian, Zhang, Xiaokang, Liu, Fangming
• Format: Article
• Language: English
• Subjects: Apoptosis; Apoptosis - genetics; Cancer; Caspase; caspases; Cell cycle; Cell cycle arrest; Cell Cycle Proteins - genetics; Cell Line, Tumor; Cyclin E - genetics; Cyclin E1; Cyclin-Dependent Kinase 2 - genetics; Cyclin-Dependent Kinase 4 - genetics; Cyclin-Dependent Kinase Inhibitor p16 - genetics; Cyclin-Dependent Kinase Inhibitor p21 - genetics; Cyclin-Dependent Kinase Inhibitor p21 - metabolism; Cyclins; Flow cytometry; G1 Phase Cell Cycle Checkpoints - genetics; Gene Expression Regulation, Neoplastic; Humans; IGFBP-3; Insulin-Like Growth Factor Binding Protein 3 - genetics; Insulin-Like Growth Factor Binding Protein 3 - metabolism; Insulin-like growth factor-binding protein 3; Insulin-like growth factors; MCF-7 Cells; Microscopes; p21; Polymerase chain reaction; proteins; quantitative polymerase chain reaction; somatomedins; Tumor cell lines; Ultrastructure; Western blotting
• ISSN: 0378-1119; 1879-0038
• DOI: 10.1016/j.gene.2012.09.080

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. ► IGFBP-3 resulted in typical apoptotic ultrastructures in A549 cells. ► IGFBP-3 could induce apoptosis in MCF-7 cells, especially the early apoptosis. ► IGFBP-3 arrested the cell cycle at G1-S phase in 786-O, A549 and MCF-7 cells. ► IGFBP-3 decreased the cyclinE1 expression and increased the p21 expression.