Abstract |
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.
|
Authors | Yao-Ping Li, Fu-Guo Tian, Peng-Cheng Shi, Ling-Yun Guo, Hai-Ming Wu, Run-Qi Chen, Jin-Ming Xue |
Journal | Asian Pacific journal of cancer prevention : APJCP
(Asian Pac J Cancer Prev)
Vol. 15
Issue 23
Pg. 10151-6
( 2014)
ISSN: 2476-762X [Electronic] Thailand |
PMID | 25556440
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Aldehydes
- Cysteine Proteinase Inhibitors
- HIF1A protein, human
- Hypoxia-Inducible Factor 1, alpha Subunit
- VEGFA protein, human
- Vascular Endothelial Growth Factor A
- SIRT3 protein, human
- Sirtuin 3
- 4-hydroxy-2-nonenal
|
Topics |
- Aldehydes
(pharmacology)
- Breast Neoplasms
(metabolism)
- Cell Line, Tumor
- Cell Proliferation
(drug effects)
- Cysteine Proteinase Inhibitors
(pharmacology)
- Female
- Gene Knockdown Techniques
- Human Umbilical Vein Endothelial Cells
- Humans
- Hypoxia-Inducible Factor 1, alpha Subunit
(drug effects, metabolism)
- MCF-7 Cells
- Neovascularization, Pathologic
(metabolism)
- Signal Transduction
- Sirtuin 3
(genetics, metabolism)
- Tumor Stem Cell Assay
- Vascular Endothelial Growth Factor A
(drug effects, metabolism)
|