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Published on: May 14, 2016
Insulin-like factor binding protein-3 promotes the G1 cell cycle arrest in several cancer cell lines
Chen Wu1, Xiaobo Liu, Yuanyuan Wang
1College of Life Sciences, Hebei University, Baoding, Hebei, 071002, PR China. dawnwuchen@163.com
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.
Insights
Insulin-like growth factor binding protein-3 (IGFBP-3) induces cancer cell apoptosis by arresting the cell cycle at the G1-S phase. This involves changes in cyclin E1 and p21 protein expression, revealing a key mechanism in cancer cell death.
Area of Science:
- Molecular Biology
- Cell Biology
- Cancer Research
Background:
- Insulin-like growth factor binding protein-3 (IGFBP-3) is a protein with known roles in inducing apoptosis in cancer cells.
- Previous research demonstrated IGFBP-3's role in apoptosis via caspase activation in 786-O cells.
Purpose of the Study:
- To investigate if IGFBP-3 induces apoptosis by causing cell cycle arrest.
- To examine this mechanism in 786-O, A549, and MCF-7 cancer cell lines.
Main Methods:
- Transmission electron microscopy to observe cellular ultrastructure.
- Flow cytometry to analyze cell cycle distribution.
- Quantitative real-time PCR and Western blot to assess protein expression levels (cyclin E1, p21).
Main Results:
- Overexpressed IGFBP-3 induced typical apoptotic ultrastructures in A549 cells.
- IGFBP-3 treatment led to G1-S phase cell cycle arrest in 786-O, A549, and MCF-7 cells.
- In A549 cells, IGFBP-3 decreased cyclin E1 and increased p21 expression.
Conclusions:
- IGFBP-3 induces apoptosis in human cancer cells through G1 cell cycle arrest.
- Cyclin E1 and p21 are key regulatory proteins involved in IGFBP-3-mediated G1 arrest and apoptosis.
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