Metformin Treatment Represses Vascular Endothelial Growth Factor Gene Transcription in MCF-7 Breast Cancer Cells
Journal Title: Open Access Journal of Oncology and Medicine - Year 2018, Vol 1, Issue 3
Abstract
Background/Aim:Targeting angiogenesis preferentially in cancer is a promising approach to improve treatment efficacy and safety. The aim of this study is investigate potential upregulation of Krüppel like factor-4(KLF-4) by inhibition of mammalian target of rapamycin (mTOR) to repress vascular endothelial growth factor (VEGF) expression in breast cancer cells. Materials and Methods: Using Western blot; bandshift assay; and Chloramphenicol acetyltransferase assay, we assessed the effect of different mTOR inhibitors on the level of mTOR pathway proteins and on KLF-4/ serum amyloid activating factor (SAF-1) SAF-1 DNA binding and consequently VEGF gene expression in MCF-7breast cancer cells. Results: mTOR inhibition increased KLF-4 level in breast cancer cells, but this inhibition, except for metformin, elicited rebound upregulation of mTOR signaling proteins. Thus metformin produced a sustained increase in KLF-4 level and concomitant disruption of SAF-1 binding to VEGF promoter with consequent inhibition of VEGF expression. Conclusion:Repurposing metformin as a potential neoadjuvant and antiangiogenic treatment could provide the basis for more effective and safer antiangiogenic treatment.
Authors and Affiliations
Mohamed Alalem, Bimal K Ray
Keywords
Related Articles
- EP ID EP586783
- DOI 10.32474/OAJOM.2018.01.000115
- Views 74
- Downloads 0
Aspirin, Vascular Disease and Cancer: 50 Years of Controversy and the Jury’s Still Out!
The story of aspirin and vascular disease starts with John O Brien, a haematologist in Portsmouth in the 1960s, who reported that the ingestion of 150mg of aspirin substantially reduced the aggregation of platelets [1]....
Permissiveness Paradox in Cell Cycle Progression Towards Genome Instability and Malignant Transformation
Dimensional representation of events actively executing the cell cycle dynamics of progression in carcinogenesis allow for a paradoxical emergence of highly permissive elements in the establishment of the mitotic spindle...
Plasma Lysophasphatidic Acid Level: A Diagnostic Tool and Benchmark for Ovarian Cancer Management
In ovarian cancer there is formation of tumor cells in ovarian tissues. Lysophosphatidic acid (LPA) motivated cell proliferation, migration and endurance by acting on its cognate G-protein-coupled receptors. Lysophosphat...
Thrombosis in Iron Deficiency and Iron Deficiency Anemia: A Review of our Cases and the Relevant Literature
We evaluated our thrombosis cases for iron deficiency (ID) or iron deficiency anemia (IDA) retrospectively and reviewed the literature. We established that iron parameters were studied in 17 of 64 patients with thrombosi...
Repurposed Drugs and Nutraceutical Supplements as Neglected Complements to Cancer Treatment
In ovarian cancer there is formation of tumor cells in ovarian tissues. Lysophosphatidic acid (LPA) motivated cell proliferation, migration and endurance by acting on its cognate G-protein-coupled receptors. Lysophosphat...