Ectopically Expressed Perforin-1 Is Proapoptotic in Tumor Cell Lines by Increasing Caspase-3 Activity and the Nuclear Translocation of Cytochrome c
| Autor: | Jing Zhao, Angang Yang, Libo Yao, Yun-Xin Cao, Yan-Ling Meng, Jun-Tang Li, Si-Yi Chen, Fang Wang, Lifeng Wang, Yan-Ming Xu, Wei-Hong Wen, Lin-Tao Jia |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Cell Physiology
Anatomy and Physiology Immunology lcsh:Medicine Fluorescent Antibody Technique Apoptosis Phosphatidylserines Cell Line Tumor Molecular Cell Biology Basic Cancer Research In Situ Nick-End Labeling Cytotoxic T cell Signaling in Cellular Processes Humans lcsh:Science Biology Apoptotic Signaling Oncogenic Signaling Multidisciplinary biology Cell Death Cell growth Caspase 3 Perforin lcsh:R Cell Cycle Degranulation Immunity Apoptosis Inducing Factor Cytochromes c Hep G2 Cells Cell cycle Signaling in Selected Disciplines digestive system diseases Cell biology Granzyme B Granzyme Oncology Cancer cell biology.protein Medicine lcsh:Q Cellular Types Research Article Signal Transduction HeLa Cells |
| Zdroj: | PLoS ONE PLoS ONE, Vol 7, Iss 7, p e40639 (2012) |
| ISSN: | 1932-6203 |
| Popis: | Perforin-1 (PRF), a cytotoxic lymphocyte pore-forming protein, plays an important role in the action of cytotoxic T cells and natural killer cells in that it causes the lysis of abnormal body cells and the elimination of virus-infected cells and tumors. Upon degranulation, PRF inserts itself into the target cell's plasma membrane, forming a pore. The subsequent translocation of pro-apoptotic granzymes (including granzyme B, A, M et al.) into the cytoplasm provides the proteases with access to numerous protein substrates that promote apoptosis after cleavage. These proteases are believed to be the main executioners of target cell apoptosis. Although the PRF and granzyme components are both critical to this process and in some way involved in inducing cell death in target cells, the inhibition of tumor growth could still be efficient in granzyme-deficient mice. It is unclear whether PRF alone can suppress tumors. In this study, we discovered that forced ectopic expression of PRF alone, in the absence of granzymes, could mediate cell death in cancer cells. Notably, transient expression of both full-length and truncated active-form PRF in human Hep G2, SK-BR-3, and HeLa cells was found to induce apparent cell growth inhibition and cell death, as evidenced by chromosome condensation and DNA fragmentation, increased caspase-3 activity, and the release of apoptosis inducing factor (AIF) and cytochrome c from the mitochondria. This PRF-induced cell death could be abrogated by pan-caspase inhibitor (Z-VAD) and mitochondria protector (TAT-BH4). The implication of these results is that ectopically expressed PRF has apoptosis-inducing abilities, and PRF alone is sufficient to induce apoptotic cell death in cells with ectopic expression. Taking this into consideration, our results suggest the possibility of using PRF as a pro-apoptotic gene for tumor therapeutics. |
| Databáze: | OpenAIRE |
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