4-Hydroxynonenal Promotes Growth and Angiogenesis of Breast Cancer Cells through HIF-1α Stabilization
| Autor: | Fu-Guo Tian, Peng-Cheng Shi, Hai-Ming Wu, Ling-Yun Guo, Jin-Ming Xue, Yao-Ping Li, Run-Qi Chen |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Vascular Endothelial Growth Factor A
Cancer Research SIRT3 Epidemiology Angiogenesis Breast Neoplasms Cysteine Proteinase Inhibitors chemistry.chemical_compound Breast cancer Cell Line Tumor Sirtuin 3 Human Umbilical Vein Endothelial Cells medicine Humans PTEN Tumor Stem Cell Assay Cell Proliferation Aldehydes Neovascularization Pathologic biology Cell growth Public Health Environmental and Occupational Health Hypoxia-Inducible Factor 1 alpha Subunit medicine.disease Vascular endothelial growth factor HIF1A Oncology chemistry Gene Knockdown Techniques MCF-7 Cells Cancer research biology.protein Female Signal Transduction Deacetylase activity |
| Zdroj: | Asian Pacific Journal of Cancer Prevention. 15:10151-10156 |
| ISSN: | 1513-7368 |
| DOI: | 10.7314/apjcp.2014.15.23.10151 |
| Popis: | 4-Hydroxynonenal (4-HNE) is a stable end product of lipid peroxidation, which has been shown to play an important role in cell signal transduction, while increasing cell growth and differentiation. 4-HNE could inhibit phosphatase and tensin homolog (PTEN) activity in hepatocytes and increased levels have been found in human invasive breast cancer. Here we report that 4-HNE increased the cell growth of breast cancer cells as revealed by colony formation assay. Moreover, vascular endothelial growth factor (VEGF) expression was elevated, while protein levels of hypoxia inducible factor 1 alpha (HIF-1α) were up-regulated. Sirtuin-3 (SIRT3), a major mitochondria NAD+-dependent deacetylase, is reported to destabilize HIF-1α. Here, 4-HNE could inhibit the deacetylase activity of SIRT3 by thiol-specific modification. We further demonstrated that the regulation by 4-HNE of levels of HIF-1α and VEGF depends on SIRT3. Consistent with this, 4-HNE could not increase the cell growth in SIRT3 knockdown breast cancer cells. Additionally, 4-HNE promoted angiogenesis and invasion of breast cancer cells in a SIRT3-dependent manner. In conclusion, we propose that 4-HNE promotes growth, invasion and angiogenesis of breast cancer cells through the SIRT3-HIF-1α-VEGF axis. |
| Databáze: | OpenAIRE |
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