Metformin Inhibits Migration and Invasion by Suppressing ROS Production and COX2 Expression in MDA-MB-231 Breast Cancer Cells

Autor: Amber Keizerweerd, Kiera Broussard, LeFontae McAtee, Demitrius Onuaguluchi, Christopher Williams, Chandler Schexnayder, Harris E. McFerrin, Anthony Poché, Shawn D. Llopis, Moamen Ismail
Rok vydání: 2018
Předmět:
0301 basic medicine
Mitochondrial ROS
Endogeny
Antioxidants
Metastasis
lcsh:Chemistry
ICAM1
0302 clinical medicine
Cell Movement
10. No inequality
lcsh:QH301-705.5
Spectroscopy
reactive oxygen species
medicine.diagnostic_test
Chemistry
General Medicine
Intercellular Adhesion Molecule-1
Metformin
3. Good health
Computer Science Applications
Chorioallantoic membrane
030220 oncology & carcinogenesis
Female
COX2
medicine.drug
Antineoplastic Agents
Breast Neoplasms
Catalysis
Dinoprostone
Article
Flow cytometry
Inorganic Chemistry
03 medical and health sciences
Cell Line
Tumor
medicine
Humans
metastasis
Viability assay
Physical and Theoretical Chemistry
Molecular Biology
Cell Proliferation
Organic Chemistry
medicine.disease
030104 developmental biology
lcsh:Biology (General)
lcsh:QD1-999
Cell culture
Cyclooxygenase 2
Cancer research
Zdroj: International Journal of Molecular Sciences
Volume 19
Issue 11
International Journal of Molecular Sciences, Vol 19, Iss 11, p 3692 (2018)
ISSN: 1422-0067
Popis: Background: Several mechanisms of action have been proposed to explain the apparent antineoplastic functions of metformin, many of which are observed at high concentrations that may not be reflective of achievable tissue concentrations. We propose that metformin at low concentrations functions to inhibit ROS production and inflammatory signaling in breast cancer, thereby reducing metastasis. Methods: Using the highly invasive MDA-MB-231 breast carcinoma model, we ascertained the impact of metformin on cell viability by DNA content analysis and fluorescent dye exclusion. Migration and invasion assays were performed using a modified Boyden chamber assay and metastasis was ascertained using the chorioallantoic membrane (CAM) assay. PGE2 production was measured by Enzyme-Linked Immunosorbent Assay (ELISA). COX2 and ICAM1 levels were determined by flow cytometry immunoassay. Results: Metformin acutely decreased cell viability and caused G2 cell cycle arrest only at high concentrations (10 mM). At 100 µ
M, however, metformin reduced ICAM1 and COX2 expression, as well as reduced PGE2 production and endogenous mitochondrial ROS production while failing to significantly impact cell viability. Consequently, metformin inhibited migration, invasion in vitro and PGE2-dependent metastasis in CAM assays. Conclusion: At pharmacologically achievable concentrations, metformin does not drastically impact cell viability, but inhibits inflammatory signaling and metastatic progression in breast cancer cells.
Databáze: OpenAIRE
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