Metformin Treatment Inhibits Motility and Invasion of Glioblastoma Cancer Cells

被引:45
作者
Al Hassan, Marwa [1 ]
Fakhoury, Isabelle [1 ]
El Masri, Zeinab [1 ]
Ghazale, Noura [1 ]
Dennaoui, Rayane [1 ]
El Atat, Oula [1 ]
Kanaan, Amjad [2 ]
El-Sibai, Mirvat [1 ]
机构
[1] Lebanese Amer Univ, Sch Arts & Sci, Dept Nat Sci, Beirut, Lebanon
[2] Univ Balamand, Fac Med & Med Sci, Dept Biomed Sci, El Kurah, Lebanon
关键词
STEM-CELLS; BREAST-CANCER; PRIMARY BRAIN; RHO GTPASES; MIGRATION; GROWTH; METASTASIS; PATHWAYS; CADHERIN;
D O I
10.1155/2018/5917470
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页数:9
相关论文
共 52 条
[1]   Glucose-6-phosphatase Is a Key Metabolic Regulator of Glioblastoma Invasion [J].
Abbadi, Sara ;
Rodarte, Julio J. ;
Abutaleb, Ameer ;
Lavell, Emily ;
Smith, Chris L. ;
Ruff, William ;
Schiller, Jennifer ;
Olivi, Alessandro ;
Levchenko, Andre ;
Guerrero-Cazares, Hugo ;
Quinones-Hinojosa, Alfredo .
MOLECULAR CANCER RESEARCH, 2014, 12 (11) :1547-1559
[2]   Brain Cancer Stem Cells in Adults and Children: Cell Biology and Therapeutic Implications [J].
Abou-Antoun, Tamara J. ;
Hale, James S. ;
Lathia, Justin D. ;
Dombrowski, Stephen M. .
NEUROTHERAPEUTICS, 2017, 14 (02) :372-384
[3]   Metformin enhanced in vitro radiosensitivity associates with G2/M cell cycle arrest and elevated adenosine-5′-monophosphateactivated protein kinase levels in glioblastoma [J].
Adeberg, Sebastian ;
Bernhardt, Denise ;
Harrabi, Semi B. ;
Nicolay, Nils H. ;
Hoerner-Rieber, Juliane ;
Koenig, Laila ;
Repka, Michael ;
Mohr, Angela ;
Abdollahi, Amir ;
Weber, Klaus-Josef ;
Debus, Juergen ;
Rieken, Stefan .
RADIOLOGY AND ONCOLOGY, 2017, 51 (04) :431-437
[4]   Metformin: an old but still the best treatment for type 2 diabetes [J].
Aguayo Rojas, Lilian Beatriz ;
Gomes, Marilia Brito .
DIABETOLOGY & METABOLIC SYNDROME, 2013, 5
[5]   Emerging role of plexins signaling in glioma progression and therapy [J].
Angelopoulou, Efthalia ;
Piperi, Christina .
CANCER LETTERS, 2018, 414 :81-87
[6]  
Armento A, 2017, GLIOBLASTOMA, P73, DOI 10.15586/codon.glioblastoma.2017.ch5
[7]   Podosome-type adhesions and focal adhesions, so alike yet so different [J].
Block, Marc R. ;
Badowski, Cedric ;
Millon-Fremillon, Angelique ;
Bouvard, Daniel ;
Bouin, Anne-Pascale ;
Faurobert, Eva ;
Gerber-Scokaert, Delphine ;
Planus, Emmanuelle ;
Albiges-Rizo, Corinne .
EUROPEAN JOURNAL OF CELL BIOLOGY, 2008, 87 (8-9) :491-506
[8]  
Carmignani M, 2014, J BIOL REG HOMEOS AG, V28, P1
[9]   Metformin Blocks Melanoma Invasion and Metastasis Development in AMPK/p53-Dependent Manner [J].
Cerezo, Michael ;
Tichet, Melanie ;
Abbe, Patricia ;
Ohanna, Mickael ;
Lehraiki, Abdelali ;
Rouaud, Florian ;
Allegra, Maryline ;
Giacchero, Damien ;
Bahadoran, Philippe ;
Bertolotto, Corine ;
Tartare-Deckert, Sophie ;
Ballotti, Robert ;
Rocchi, Stephane .
MOLECULAR CANCER THERAPEUTICS, 2013, 12 (08) :1605-1615
[10]   Dimethylbiguanide inhibits cell respiration via an indirect effect targeted on the respiratory chain complex I [J].
El-Mir, MY ;
Nogueira, V ;
Fontaine, E ;
Avéret, N ;
Rigoulet, M ;
Leverve, X .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (01) :223-228