Metformin Treatment Inhibits Motility and Invasion of Glioblastoma Cancer Cells
Abstract
Glioblastoma multiforme (GBM) is one of the most common and deadliest cancers of the central nervous system (CNS). GBMs high ability to infiltrate healthy brain tissues makes it difficult to remove surgically and account for its fatal outcomes. To improve the chances of survival, it is critical to screen for GBM-targeted anticancer agents with anti-invasive and antimigratory potential. Metformin, a commonly used drug for the treatment of diabetes, has recently emerged as a promising anticancer molecule. This prompted us, to investigate the anticancer potential of metformin against GBMs, specifically its effects on cell motility and invasion. The results show a significant decrease in the survival of SF268 cancer cells in response to treatment with metformin. Furthermore, metformin’s efficiency in inhibiting 2D cell motility and cell invasion in addition to increasing cellular adhesion was also demonstrated in SF268 and U87 cells. Finally, AKT inactivation by downregulation of the phosphorylation level upon metformin treatment was also evidenced. In conclusion, this study provides insights into the anti-invasive antimetastatic potential of metformin as well as its underlying mechanism of action.
- Authors:
-
[1];
[1];
[1];
[2];
[1]
- Department of Natural Sciences, School of Arts and Sciences, Lebanese American University, Beirut, Lebanon
- Department of Biomedical Sciences, Faculty of Medicine and Medical Sciences, University of Balamand, El-Kurah, Lebanon
- Publication Date:
- Sponsoring Org.:
- USDOE Office of Electricity (OE), Advanced Grid Research & Development. Power Systems Engineering Research
- OSTI Identifier:
- 1457218
- Resource Type:
- Published Article
- Journal Name:
- Analytical Cellular Pathology
- Additional Journal Information:
- Journal Name: Analytical Cellular Pathology Journal Volume: 2018; Journal ID: ISSN 2210-7177
- Publisher:
- Hindawi Publishing Corporation
- Country of Publication:
- Country unknown/Code not available
- Language:
- English
Citation Formats
Al Hassan, Marwa, Fakhoury, Isabelle, El Masri, Zeinab, Ghazale, Noura, Dennaoui, Rayane, El Atat, Oula, Kanaan, Amjad, and El-Sibai, Mirvat. Metformin Treatment Inhibits Motility and Invasion of Glioblastoma Cancer Cells. Country unknown/Code not available: N. p., 2018.
Web. doi:10.1155/2018/5917470.
Al Hassan, Marwa, Fakhoury, Isabelle, El Masri, Zeinab, Ghazale, Noura, Dennaoui, Rayane, El Atat, Oula, Kanaan, Amjad, & El-Sibai, Mirvat. Metformin Treatment Inhibits Motility and Invasion of Glioblastoma Cancer Cells. Country unknown/Code not available. doi:https://doi.org/10.1155/2018/5917470
Al Hassan, Marwa, Fakhoury, Isabelle, El Masri, Zeinab, Ghazale, Noura, Dennaoui, Rayane, El Atat, Oula, Kanaan, Amjad, and El-Sibai, Mirvat. Tue .
"Metformin Treatment Inhibits Motility and Invasion of Glioblastoma Cancer Cells". Country unknown/Code not available. doi:https://doi.org/10.1155/2018/5917470.
@article{osti_1457218,
title = {Metformin Treatment Inhibits Motility and Invasion of Glioblastoma Cancer Cells},
author = {Al Hassan, Marwa and Fakhoury, Isabelle and El Masri, Zeinab and Ghazale, Noura and Dennaoui, Rayane and El Atat, Oula and Kanaan, Amjad and El-Sibai, Mirvat},
abstractNote = {Glioblastoma multiforme (GBM) is one of the most common and deadliest cancers of the central nervous system (CNS). GBMs high ability to infiltrate healthy brain tissues makes it difficult to remove surgically and account for its fatal outcomes. To improve the chances of survival, it is critical to screen for GBM-targeted anticancer agents with anti-invasive and antimigratory potential. Metformin, a commonly used drug for the treatment of diabetes, has recently emerged as a promising anticancer molecule. This prompted us, to investigate the anticancer potential of metformin against GBMs, specifically its effects on cell motility and invasion. The results show a significant decrease in the survival of SF268 cancer cells in response to treatment with metformin. Furthermore, metformin’s efficiency in inhibiting 2D cell motility and cell invasion in addition to increasing cellular adhesion was also demonstrated in SF268 and U87 cells. Finally, AKT inactivation by downregulation of the phosphorylation level upon metformin treatment was also evidenced. In conclusion, this study provides insights into the anti-invasive antimetastatic potential of metformin as well as its underlying mechanism of action.},
doi = {10.1155/2018/5917470},
journal = {Analytical Cellular Pathology},
number = ,
volume = 2018,
place = {Country unknown/Code not available},
year = {2018},
month = {6}
}
Free Publicly Available Full Text
Publisher's Version of Record
DOI: https://doi.org/10.1155/2018/5917470
DOI: https://doi.org/10.1155/2018/5917470
Other availability
Search WorldCat to find libraries that may hold this journal
Cited by: 1 work
Citation information provided by
Web of Science
Web of Science
Save to My Library
You must Sign In or Create an Account in order to save documents to your library.
Works referenced in this record:
Metformin inhibits leptin-induced growth and migration of glioblastoma cells
journal, August 2012
- Ferla, Rita; Haspinger, Eva; Surmacz, Eva
- Oncology Letters, Vol. 4, Issue 5
Metformin represses cancer cells via alternate pathways in N-cadherin expressing vs. N-cadherin deficient cells
journal, August 2015
- Ge, Rongbin; Wang, Zongwei; Wu, Shulin
- Oncotarget, Vol. 6, Issue 30
Low Concentrations of Metformin Selectively Inhibit CD133+ Cell Proliferation in Pancreatic Cancer and Have Anticancer Action
journal, May 2013
- Gou, Shanmiao; Cui, Pengfei; Li, Xiangsheng
- PLoS ONE, Vol. 8, Issue 5
Emerging role of plexins signaling in glioma progression and therapy
journal, February 2018
- Angelopoulou, Efthalia; Piperi, Christina
- Cancer Letters, Vol. 414
Metformin enhanced in vitro radiosensitivity associates with G2/M cell cycle arrest and elevated adenosine-5’-monophosphate-activated protein kinase levels in glioblastoma
journal, November 2017
- Adeberg, Sebastian; Bernhardt, Denise; Harrabi, Semi B.
- Radiology and Oncology, Vol. 51, Issue 4
Metformin — a new old drug
journal, August 2017
- Wróbel, Marta Patrycja; Marek, Bogdan; Kajdaniuk, Dariusz
- Endokrynologia Polska, Vol. 68, Issue 4
Anticancer effects of metformin on neuroendocrine tumor cells in vitro [Anticancer effects of metformin on neuroendocrine tumor cells in vitro]
journal, July 2014
- Vlotides, George; Tanyeri,, Ayse; Spampatti,, Matilde
- HORMONES
Kefir exhibits anti-proliferative and pro-apoptotic effects on colon adenocarcinoma cells with no significant effects on cell migration and invasion
journal, September 2014
- Khoury, Nathalie; El-Hayek, Stephany; Tarras, Omayr
- International Journal of Oncology, Vol. 45, Issue 5
Metformin inhibits proliferation and migration of glioblastoma cells independently of TGF-β2
journal, April 2016
- Seliger, Corinna; Meyer, Anne-Louise; Renner, Kathrin
- Cell Cycle, Vol. 15, Issue 13
Glucose-6–phosphatase Is a Key Metabolic Regulator of Glioblastoma Invasion
journal, July 2014
- Abbadi, Sara; Rodarte, Julio J.; Abutaleb, Ameer
- Molecular Cancer Research, Vol. 12, Issue 11
American Brain Tumor Association Adolescent and Young Adult Primary Brain and Central Nervous System Tumors Diagnosed in the United States in 2008-2012
journal, December 2015
- Ostrom, Quinn T.; Gittleman, Haley; de Blank, Peter M.
- Neuro-Oncology, Vol. 18, Issue suppl 1
Hallmarks of Cancer: The Next Generation
journal, March 2011
- Hanahan, Douglas; Weinberg, Robert A.
- Cell, Vol. 144, Issue 5
Signaling networks of Rho GTPases in cell motility
journal, October 2013
- Hanna, Samer; El-Sibai, Mirvat
- Cellular Signalling, Vol. 25, Issue 10
Temozolomide in combination with metformin act synergistically to inhibit proliferation and expansion of glioma stem-like cells
journal, March 2016
- Yu, Zhiyun; Zhao, Gang; Li, Pengliang
- Oncology Letters, Vol. 11, Issue 4
Metformin: an old but still the best treatment for type 2 diabetes
journal, February 2013
- Rojas, Lilian Beatriz Aguayo; Gomes, Marilia Brito
- Diabetology & Metabolic Syndrome, Vol. 5, Issue 1
Brain Cancer Stem Cells in Adults and Children: Cell Biology and Therapeutic Implications
journal, April 2017
- Abou-Antoun, Tamara J.; Hale, James S.; Lathia, Justin D.
- Neurotherapeutics, Vol. 14, Issue 2
Metformin use improves the survival of diabetic combined small-cell lung cancer patients
journal, May 2015
- Kong, Fanming; Gao, Fangfang; Liu, Honggen
- Tumor Biology, Vol. 36, Issue 10
Regulation of cell adhesion and migration by cell-derived matrices
journal, October 2013
- Kutys, Matthew L.; Doyle, Andrew D.; Yamada, Kenneth M.
- Experimental Cell Research, Vol. 319, Issue 16
Podosome-type adhesions and focal adhesions, so alike yet so different
journal, September 2008
- Block, M.; Badowski, C.; Millonfremillon, A.
- European Journal of Cell Biology, Vol. 87, Issue 8-9
StarD13 is a tumor suppressor in breast cancer that regulates cell motility and invasion
journal, March 2014
- Hanna, Samer; Khalil, Bassem; Nasrallah, Anita
- International Journal of Oncology, Vol. 44, Issue 5
Glioma-Initiating Cell Elimination by Metformin Activation of FOXO3 via AMPK
journal, November 2012
- Sato, Atsushi; Sunayama, Jun; Okada, Masashi
- STEM CELLS Translational Medicine, Vol. 1, Issue 11
Molecular Pathways: Preclinical Models and Clinical Trials with Metformin in Breast Cancer
journal, March 2014
- Thompson, A. M.
- Clinical Cancer Research, Vol. 20, Issue 10
Metformin and Ara-a Effectively Suppress Brain Cancer by Targeting Cancer Stem/Progenitor Cells
journal, November 2015
- Mouhieddine, Tarek H.; Nokkari, Amaly; Itani, Muhieddine M.
- Frontiers in Neuroscience, Vol. 9
Metformin and temozolomide act synergistically to inhibit growth of glioma cells and glioma stem cells <i>in vitro</i> and <i>in vivo</i>
journal, September 2015
- Yu, Zhiyun; Zhao, Gang; Xie, Guifang
- Oncotarget, Vol. 6, Issue 32
Exploring the role of metformin in anticancer treatments: A systematic review
journal, January 2014
- Miranda, V. C.; Barroso-Sousa, R.; Glasberg, J.
- Drugs of Today, Vol. 50, Issue 9
Dimethylbiguanide Inhibits Cell Respiration via an Indirect Effect Targeted on the Respiratory Chain Complex I
journal, January 2000
- El-Mir, Mohamad-Yehia; Nogueira, Véronique; Fontaine, Eric
- Journal of Biological Chemistry, Vol. 275, Issue 1
Metformin attenuates ovarian cancer cell growth in an AMP-kinase dispensable manner
journal, October 2009
- Rattan, R.; Giri, S.; Hartmann, L. C.
- Journal of Cellular and Molecular Medicine, Vol. 15, Issue 1
Cancer stem cells in glioblastoma
journal, June 2015
- Lathia, Justin D.; Mack, Stephen C.; Mulkearns-Hubert, Erin E.
- Genes & Development, Vol. 29, Issue 12
Differential sensitivities of glioblastoma cell lines towards metabolic and signaling pathway inhibitions
journal, August 2013
- Kennedy, Colin R.; Tilkens, Sarah B.; Guan, Hong
- Cancer Letters, Vol. 336, Issue 2
Metformin: clinical use in type 2 diabetes
journal, August 2017
- Sanchez-Rangel, Elizabeth; Inzucchi, Silvio E.
- Diabetologia, Vol. 60, Issue 9
Glioblastoma and Other Malignant Gliomas: A Clinical Review
journal, November 2013
- Omuro, Antonio
- JAMA, Vol. 310, Issue 17
Cisplatin Combined with Metformin Inhibits Migration and Invasion of Human Nasopharyngeal Carcinoma Cells by Regulating E-cadherin and MMP-9
journal, May 2014
- Sun, Xiao-Jin; Zhang, Pei; Li, Hai-Hui
- Asian Pacific Journal of Cancer Prevention, Vol. 15, Issue 9
Metformin: A Potential Therapeutic Agent for Recurrent Colon Cancer
journal, January 2014
- Nangia-Makker, Pratima; Yu, Yingjie; Vasudevan, Anita
- PLoS ONE, Vol. 9, Issue 1
Invadopodia, Regulation, and Assembly in Cancer Cell Invasion
journal, June 2014
- Saykali, Bechara A.; El-Sibai, Mirvat
- Cell Communication & Adhesion, Vol. 21, Issue 4
Metformin selectively affects human glioblastoma tumor-initiating cell viability: A role for metformin-induced inhibition of Akt
journal, January 2013
- Würth, Roberto; Pattarozzi, Alessandra; Gatti, Monica
- Cell Cycle, Vol. 12, Issue 1
Metformin Blocks Melanoma Invasion and Metastasis Development in AMPK/p53-Dependent Manner
journal, June 2013
- Cerezo, M.; Tichet, M.; Abbe, P.
- Molecular Cancer Therapeutics, Vol. 12, Issue 8
Metformin Inhibits Growth of Human Glioblastoma Cells and Enhances Therapeutic Response
journal, April 2015
- Sesen, Julie; Dahan, Perrine; Scotland, Sarah J.
- PLOS ONE, Vol. 10, Issue 4
CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2009–2013
journal, October 2016
- Ostrom, Quinn T.; Gittleman, Haley; Xu, Jordan
- Neuro-Oncology, Vol. 18, Issue suppl_5
Metformin Is an AMP Kinase–Dependent Growth Inhibitor for Breast Cancer Cells
journal, October 2006
- Zakikhani, Mahvash; Dowling, Ryan; Fantus, I. George
- Cancer Research, Vol. 66, Issue 21
Metformin inhibits glioma cell U251 invasion by downregulation of fibulin-3
journal, January 2013
- Gao, Lian-Bo; Tian, Shen; Gao, Hong-Hua
- NeuroReport, Vol. 24, Issue 10
Rho GTPases in primary brain tumor malignancy and invasion
journal, April 2012
- Khalil, Bassem D.; El-Sibai, Mirvat
- Journal of Neuro-Oncology, Vol. 108, Issue 3
Metformin inhibits the development and metastasis of ovarian cancer
journal, June 2012
- Wu, Buchu; Li, Shu; Sheng, Lili
- Oncology Reports, Vol. 28, Issue 3
Effect of metformin on the human T98G glioblastoma multiforme cell line
journal, March 2014
- Ucbek, Alİ; ÖZÜNal, Zeynep GÜNeŞ; Uzun, ÖZge
- Experimental and Therapeutic Medicine, Vol. 7, Issue 5
Dual antiglioma action of metformin: cell cycle arrest and mitochondria-dependent apoptosis
journal, April 2007
- Isakovic, A.; Harhaji, L.; Stevanovic, D.
- Cellular and Molecular Life Sciences, Vol. 64, Issue 10
Metformin against Cancer Stem Cells through the Modulation of Energy Metabolism: Special Considerations on Ovarian Cancer
journal, January 2014
- Kim, Tae Hun; Suh, Dong Hoon; Kim, Mi-Kyung
- BioMed Research International, Vol. 2014
Metformin inhibits hepatic gluconeogenesis in mice independently of the LKB1/AMPK pathway via a decrease in hepatic energy state
journal, July 2010
- Foretz, Marc; Hébrard, Sophie; Leclerc, Jocelyne
- Journal of Clinical Investigation, Vol. 120, Issue 7
The mechanisms of action of metformin
journal, August 2017
- Rena, Graham; Hardie, D. Grahame; Pearson, Ewan R.
- Diabetologia, Vol. 60, Issue 9
Metformin treatment reduces temozolomide resistance of glioblastoma cells
journal, October 2016
- Yang, Seung Ho; Li, Shenglan; Lu, Guangrong
- Oncotarget, Vol. 7, Issue 48