The metformin influence on proliferation cells of brain tumor in cell culture in vitro
DOI:
https://doi.org/10.25305/unj.59045Keywords:
метформин, опухоли мозга, глиобластомы, культура клеток in vitrо, экспериментAbstract
Introduction. Today scientists pay much attention to studies of antitumor effect of anti-diabetes medicine metformin on different human tumors, including brain tumor.
The aim of research was to study influence of metformin on glial tumors in cell culture in vitro.
Materials and methods. Antiproliferation and cytotoxical activity of metformin on different brain tumors was studied in cell culture in vitro during 24 h at 37°C with of 0.1% of trypan blue solution. 26 different brain tumors were studied.
Results. Antidiabetes medicine metformin had antiproliferation and cytotoxical activity on cells of different brain tumor in suspension cell culture in vitro. Antitumor effect depended on the medicine dose, large doses —100 mcg/ml were more effective than small ones — 1 mcg/ml. Malignant brain gliomas (glioblastomas) were more sensitive to metformin’s action than astrocytomas of I–II degrees of anaplasia.
Conclusion. The obtained data let us recommend metformin use in neurooncology on stages of combined treatment.
References
1. Dilman V. Ageing, metabolic immunodepression and carcinogenesis. Mechanisms of Ageing and Development. 1978;8:153-173. [CrossRef] [PubMed]
2. Dilman V. Age-associated elevation of hypothalamic threshold to feedback control, and its role in development, ageing, and disease. The Lancet. 1971;297(7711):1211-1219. [CrossRef] [PubMed]
3. Pollak M. Metformin and Other Biguanides in Oncology: Advancing the Research Agenda. Cancer Prevention Research. 2010;3(9):1060-1065. [CrossRef] [PubMed]
4. Anisimov V, Egormin P, Piskunova T et al. Metformin extends life span of HER-2/neu transgenic mice and in combination with melatonin inhibits growth of transplantable tumors in vivo. Cell Cycle. 2010;9(1):188-197. [CrossRef] [PubMed]
5. Martin-Castillo B, Vazquez-Martin A, Oliveras-Ferraros C, Menendez J. Metformin and cancer: Doses, mechanisms and the dandelion and hormetic phenomena. Cell Cycle. 2010;9(6):1057-1064. [CrossRef] [PubMed]
6. Vazquez-Martin A, Oliveras-Ferraros C, Cufi S, Martin-Castillo B, A. Menendez J. Metformin and Energy Metabolism in Breast Cancer: From Insulin Physiology to Tumour-initiating Stem Cells. CMM. 2010;10(7):674-691. [CrossRef] [PubMed]
7. Dilman V, Anisimov V. Effect of treatment with phenformin, diphenylhydantoin or L-dopa on life span and tumour incidence in C3H/Sn mice. Gerontology. 1980;26(5):241-246. [CrossRef] [PubMed]
8. Anisimov VN. [Effect of buformin and diphenylhydantoin on the life span, estrous function and spontaneous tumor incidence in rats]. Vopr Onkol. 1980;26(6):42-8. Russian. [PubMed]
9. Dil'man VM, Bershteĭn LM, Zabezhinskiĭ MA, Aleksandrov VA. [Effect of phenformin on mammary gland tumor induction in rats]. Vopr Onkol. 1974;20(9):94-8. Russian. [PubMed]
10. Anisimov V, Ostroumova M, Dil'man V. Inhibition of the carcinogenic effect of 7,12-dimethylbenz(a)anthracene in female rats by buformin, phenytoin, pineal polypeptide extract, and L-dopa. Bulletin of Experimental Biology and Medicine. 1980;89(6):819-822. [CrossRef] [PubMed]
11. Vinnitskii VB, Iakimenko VA. [Effect of fenformin, L-DOPA and para-chlorophenylalanine on the immunological reactivity and chemical carcinogenesis in BALB/c mice]. Vopr Onkol. 1981;27(6):45-50. Russian. [PubMed]
12. Anisimov VN, Pozharisskiĭ KM, Dil'man VM. [Effect of fenformin on the blastomogenic action of 1,2-dimethylhydrazine in rats]. Vopr Onkol. 1980;26(8):54-8. Russian. [PubMed]
13. Saydah S. Abnormal Glucose Tolerance and the Risk of Cancer Death in the United States. American Journal of Epidemiology. 2003;157(12):1092-1100. [CrossRef] [PubMed]
14. Lipscombe L, Goodwin P, Zinman B, McLaughlin J, Hux J. Diabetes mellitus and breast cancer: a retrospective population-based cohort study. Breast Cancer Res Treat. 2006;98(3):349-356. [CrossRef] [PubMed]
15. Patel T, Hruby G, Badani K, Abate-Shen C, McKiernan J. Clinical Outcomes After Radical Prostatectomy in Diabetic Patients Treated With Metformin. Urology. 2010;76(5):1240-1244. [CrossRef] [PubMed]
16. Dowling R, Zakikhani M, Fantus I, Pollak M, Sonenberg N. Metformin Inhibits Mammalian Target of Rapamycin Dependent Translation Initiation in Breast Cancer Cells. Cancer Research. 2007;67(22):10804-10812. [CrossRef] [PubMed]
17. Zakikhani M, Dowling R, Fantus I, Sonenberg N, Pollak M. Metformin Is an AMP Kinase-Dependent Growth Inhibitor for Breast Cancer Cells. Cancer Research. 2006;66(21):10269-10273. [CrossRef] [PubMed]
18. Buzzai M, Jones R, Amaravadi R et al. Systemic Treatment with the Antidiabetic Drug Metformin Selectively Impairs p53-Deficient Tumor Cell Growth. Cancer Research. 2007;67(14):6745-6752. [CrossRef] [PubMed]
19. Isakovic A, Harhaji L, Stevanovic D et al. Dual antiglioma action of metformin: cell cycle arrest and mitochondria-dependent apoptosis. Cell Mol Life Sci. 2007;64(10):1290-1302. [CrossRef] [PubMed]
20. Gotlieb W, Saumet J, Beauchamp M et al. In vitro metformin anti-neoplastic activity in epithelial ovarian cancer. Gynecologic Oncology. 2008;110(2):246-250. [PubMed]
21. Hirsch H, Iliopoulos D, Tsichlis P, Struhl K. Metformin Selectively Targets Cancer Stem Cells, and Acts Together with Chemotherapy to Block Tumor Growth and Prolong Remission. Cancer Research. 2009;69(19):7507-7511. [CrossRef] [PubMed]
22. Vazquez-Martin A, Oliveras-Ferraros C, Cufí S, Del Barco S, Martin-Castillo B, Menendez J. Metformin regulates breast cancer stem cello ntogeny by transcriptional regulation of the epithelial-mesenchymal transition (EMT) status. Cell Cycle. 2010;9(18):3831-3838. [PubMed]
23. Liu B, Fan Z, Edgerton S et al. Metformin induces unique biological and molecular responses in triple negative breast cancer cells. Cell Cycle. 2009;8(13):2031-2040. [CrossRef] [PubMed]
24. Dowling R, Goodwin P, Stambolic V. Understanding the benefit of metformin use in cancer treatment. BMC Medicine. 2011;9(1):33. [PubMed]
25. Belfiore A, Frasca F. IGF and Insulin Receptor Signaling in Breast Cancer. J Mammary Gland Biol Neoplasia. 2008;13(4):381-406. [CrossRef] [PubMed]
26. Frasca F, Pandini G, Sciacca L et al. The role of insulin receptors and IGF-I receptors in cancer and other diseases. Archives of Physiology and Biochemistry. 2008;114(1):23-37. [CrossRef] [PubMed]
27. Mulligan A, O’Malley F, Ennis M, Fantus I, Goodwin P. Insulin receptor is an independent predictor of a favorable outcome in early stage breast cancer. Breast Cancer Res Treat. 2007;106(1):39-47. [CrossRef] [PubMed]
28. Soritau O, Tomuleasa C, Aldea M, Petrushev B, Susman S, Gheban D, Ioani H, Cosis A, Brie I, Irimie A, Kacso G, Florian IS. Metformin plus temozolomide-based chemotherapy as adjuvant treatment for WHO grade III and IV malignant gliomas. J BUON. 2011 Apr-Jun;16(2):282-9. [PubMed]
29. Lisyanyy M, Prymushko L, Lisyanyy O. Doslidzhennya protypukhlynnoyi diyi deyakykh imunomodulyatoriv [The study of some antitumor immunomodulators]. Ukrainian Neurosurgical Journal. 2006;1:35-36. Ukrainian.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2012 Nikolay Lisianyi, L. Sulenko, Oleksandr Lisianyi, Antonina Klyuchnikova
This work is licensed under a Creative Commons Attribution 4.0 International License.
Ukrainian Neurosurgical Journal abides by the CREATIVE COMMONS copyright rights and permissions for open access journals.
Authors, who are published in this Journal, agree to the following conditions:
1. The authors reserve the right to authorship of the work and pass the first publication right of this work to the Journal under the terms of Creative Commons Attribution License, which allows others to freely distribute the published research with the obligatory reference to the authors of the original work and the first publication of the work in this Journal.
2. The authors have the right to conclude separate supplement agreements that relate to non-exclusive work distribution in the form of which it has been published by the Journal (for example, to upload the work to the online storage of the Journal or publish it as part of a monograph), provided that the reference to the first publication of the work in this Journal is included.
