Volume 14, Issue 9 (9-2016)                   IJRM 2016, 14(9): 577-582 | Back to browse issues page

XML Persian Abstract Print

Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
Hashemnia S M R, Atari-Hajipirloo S, Roshan- Milani S, Valizadeh N, Mahabadi S, Kheradmand F. Imatinib alters cell viability but not growth factors levels in TM4 Sertoli cells. IJRM 2016; 14 (9) :577-582
URL: http://ijrm.ir/article-1-784-en.html
Imatinib alters cell viability but not growth factors levels in TM4 Sertoli cells
Seyyed Mohammad Reza Hashemnia1 , Somayeh Atari-Hajipirloo2 , Shiva Roshan- Milani3 , Nasim Valizadeh4 , Sonya Mahabadi2 , Fatemeh Kheradmand * 5
1- Department of Biochemistry, Tehran University of Medical Sciences, Tehran, Iran
2- Department of Biochemistry, Urmia University of Medical Sciences, Urmia, Iran
3- Department of Physiology, Cellular and Molecular Research Center, Urmia University of Medical Sciences, Urmia, Iran
4- Hematology-Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran
5- Department of Biochemistry, Cellular and Molecular and Solid Tumor research centers, Urmia University of Medical Sciences, Urmia, Iran , fkheradmand@yahoo.com
Abstract:   (2651 Views)
Background: The anticancer agent imatinib (IM) is a small molecular analog ofATP that inhibits tyrosine kinase activity of platelet derived growth factors (PDGFs)and stem cell factor (SCF) receptor in cancer cells. However these factors have a keyrole in regulating growth and development of normal Sertoli, Leydig and germcells.
Objective: The aim of this study was to determine cell viability, PDGF and SCFlevels in mouse normal Sertoli cells exposed to IM.
Materials and Methods: In this experimental study, the mouse TM4 Sertoli cellswere treated with 0, 2.5, 5, 10 and 20 μM IM for 2, 4 or 6 days. The cell viabilityand growth factors levels were assessed by MTT and ELISA methods, respectively.For statistical analysis, One-Way ANOVA was performed.
Results: IM showed significant decrease in Sertoli cell viability compared to controlgroup (p=0.001). However, IM increased PDGF and SCF level insignificantly(p>0.05).
Conclusion: Results suggested that IM treatment induced a dose dependentreduction of cell viability in Sertoli cells. It seems that treatment with this anticancerdrug is involved in the fertility process. Further studies are needed to evaluate therole of PDGF and SCF in this cell.
Keywords: Cell viability, Imatinib mesylate, Sertoli cells, Platelet derived growth factor, Stem cell factor.
Full-Text [PDF 293 kb]   (892 Downloads) |   |   Full-Text (HTML)  (403 Views)  
Type of Study: Original Article |
References
1. Lindberg N, Holland EC. PDGF in gliomas: more than just a growth factor? Upsala J Med Sci 2012; 117: 92-98. [DOI:10.3109/03009734.2012.654860]
2. Nurmio M, Kallio J, Toppari J, Jahnukainen K. Adult reproductive functions after early postnatal inhibition by imatinib of the two receptor tyrosine kinases, c-kit and PDGFR, in the rat testis. Reprod Toxicol 2008; 25: 442-446. [DOI:10.1016/j.reprotox.2008.03.004]
3. Basciani S, Mariani S, Arizzi M, Ulisse S, Rucci N, Jannini EA, et al. Expression of platelet-derived growth factor-A (PDGF-A), PDGF-B, and PDGF receptor-alpha and -beta during human testicular development and disease. J Clin Endocrinol Metab 2002; 87: 2310-2319.
4. Rato L, Alves MG, Socorro S, Duarte AI, Cavaco JE, Oliveira PF. Metabolic regulation is important for spermatogenesis. Nat Rev Urol 2012; 9: 330-338. [DOI:10.1038/nrurol.2012.77]
5. Kim Y, Kobayashi A, Sekido R, DiNapoli L, Brennan J, Chaboissier MC, et al. Fgf9 and Wnt4 act as antagonistic signals to regulate mammalian sex determination. PLoS Biol 2006; 4: e187. [DOI:10.1371/journal.pbio.0040187]
6. Gnessi L, Fabbri A, Spera G. Gonadal Peptides as Mediators of Development and Functional Control of the Testis: An Integrated System with Hormones and Local Environment. Endocr Rev 1997; 18: 541-609. [DOI:10.1210/er.18.4.541]
7. Schmidt M, Loffler G. Induction of aromatase activity in human adipose tissue stromal cells by extracellular nucleotides-evidence for P2-purinoceptors in adipose tissue. Eur J Biochem 1998; 252: 147-154. [DOI:10.1046/j.1432-1327.1998.2520147.x]
8. Cardoso HJ, Figueira MI, Correia S, Vaz CV, Socorro S. The SCF/c-KIT system in the male: Survival strategies in fertility and cancer. Mol Reprod Dev 2014; 81: 1064-1079. [DOI:10.1002/mrd.22430]
9. Blanchard KT, Lee J, Boekelheide K. Leuprolide, a gonadotropin-releasing hormone agonist, reestablishes spermatogenesis after 2,5-hexanedione-induced irreversible testicular injury in the rat, resulting in normalized stem cell factor expression. Endocrinology 1998; 139: 236-244. [DOI:10.1210/endo.139.1.5678]
10. Strohmeyer T, Peter S, Hartmann M, Munemitsu S, Ackermann R, Ullrich A, et al. Expression of the hst-1 and c-kit protooncogenes in human testicular germ cell tumors. Cancer Res 1991; 51: 1811-1816.
11. Tajima Y, Onoue H, Kitamura Y, Nishimune Y. Biologically active kit ligand growth factor is produced by mouse Sertoli cells and is defective in SId mutant mice. Development 1991; 113: 1031-1035.
12. Hess RA, de Franca LR. Spermatogenesis and cycle of the seminiferous epithelium. Molecular mechanisms in spermatogenesis. Springer; 2008: 1-15.
13. Sandlow JI, Feng HL, Sandra A. Localization and expression of the c-kit receptor protein in human and rodent testis and sperm. Urology 1997; 49: 494-500. [DOI:10.1016/S0090-4295(96)00494-3]
14. Gambacorti-Passerini C, Tornaghi L, Cavagnini F, Rossi P, Pecori-Giraldi F, Mariani L, et al. Gynaecomastia in men with chronic myeloid leukaemia after imatinib. Lancet 2003; 361: 1954-1986. [DOI:10.1016/S0140-6736(03)13554-4]
15. Hou Z, Zhu HL, Liu T. Effects of imatinib mesylate on the levels of endocrine hormones. Chinese J Hematol 2013; 34: 762-766.
16. Ghalaut VS, Prakash G, Bansal P, Dahiya K, Dokwal S, Ghalaut PS, et al. Effect of imatinib on male reproductive hormones in BCR-ABL positive CML patients: A preliminary report. J Oncol Pharm Pract 2013; 20: 243-248. [DOI:10.1177/1078155213500686]
17. Prasad AM, Ramnarayan K, Nalini K, Bairy KL. Effect of imatinib on the biochemical parameters of the reproductive function in male Swiss albino mice. Indian J Pharmacol 2011; 43: 389-392. [DOI:10.4103/0253-7613.83107]
18. Schultheis B, Nijmeijer BA, Yin H, Gosden RG, Melo JV. Imatinib mesylate at therapeutic doses has no impact on folliculogenesis or spermatogenesis in a leukaemic mouse model. Leukemia Res 2012; 36: 271-274. [DOI:10.1016/j.leukres.2011.09.025]
19. Codrington AM, Hales BF, Robaire B. Exposure of male rats to cyclophosphamide alters the chromatin structure and basic proteome in spermatozoa. Hum Reprod 2007; 22: 1431-1442. [DOI:10.1093/humrep/dem002]
20. Howell SJ, Shalet SM. Spermatogenesis after cancer treatment: damage and recovery. J Natl Cancer Inst Monogr 2005; 34: 12-17. [DOI:10.1093/jncimonographs/lgi003]
21. Mohammadnejad D, Abedelahi A, Soleimani-Rad J, Mohammadi-Roshandeh A, Rashtbar M, Azami A. Degenerative effect of Cisplatin on testicular germinal epithelium. Adv Pharm Bull 2012; 2: 173-177.
22. Kheradmand F, Hashemnia SM, Valizadeh N, Roshan-Milani S. The Effects of Imatinib Mesylate on Cellular Viability, Platelet Derived Growth Factor and Stem Cell Factor in Mouse Testicular Normal Leydig Cells. J Reprod Infertil 2016; 17: 82-87.
23. Nurmio M, Kallio J, Adam M, Mayerhofer A, Toppari J, Jahnukainen K. Peritubular myoid cells have a role in postnatal testicular growth. Spermatogenesis 2012; 2: 79-87. [DOI:10.4161/spmg.20067]
24. Basciani S, Brama M, Mariani S, De Luca G, Arizzi M, Vesci L, et al. Imatinib mesylate inhibits Leydig cell tumor growth: evidence for in vitro and in vivo activity. Cancer Res 2005; 65: 1897-1903. [DOI:10.1158/0008-5472.CAN-04-2181]
25. Shu LL, Jiang QL, Meng FY, Yang M. Molecular mechanism of imatinib-induced thrombocytopenia in treatment of patients with CML. J Exp Hematol 2011; 19: 1314-1318.
26. Nurmio M, Toppari J, Zaman F, Andersson AM, Paranko J, Soder O, et al. Inhibition of tyrosine kinases PDGFR and C-Kit by imatinib mesylate interferes with postnatal testicular development in the rat. Int J Androl 2007; 30: 366-376. [DOI:10.1111/j.1365-2605.2007.00755.x]
27. Prasad AM, Ramnarayan K, Nalini K, Bairy KL. Effect of imatinib on the biochemical parameters of the reproductive function in male Swiss albino mice. Indian J Pharmacol 2011; 43: 389-392. [DOI:10.4103/0253-7613.83107]
28. Yaghmaei P, Parivar K, Gharibi A, Nabiuni M. The biological effects of imatinib on male fertility of Wistar rats. Int J Fertil Steril 2009; 3: 135-142.
29. Nurmio M, Kallio J, Toppari J, Jahnukainen K. Adult reproductive functions after early postnatal inhibition by imatinib of the two receptor tyrosine kinases, c-kit and PDGFR, in the rat testis. Reprod Toxicol 2008; 25: 442-446. [DOI:10.1016/j.reprotox.2008.03.004]
30. Hashemnia SMR, Kheradmand F, Noori N, Roshan-Milani S. Inhibition of growth factor signaling pathways by imatinib mesylate in mouse normal leydig cells. J Urmia Univ Med Sci 2013; 24: 718.
31. Fitter S, Vandyke K, Gronthos S, Zannettino AC. Suppression of PDGF-induced PI3 kinase activity by imatinib promotes adipogenesis and adiponectin secretion. J Mol Endocrinol 2012; 48: 229-240. [DOI:10.1530/JME-12-0003]
32. Yan W, Kero J, Huhtaniemi I, Toppari J. Stem cell factor functions as a survival factor for mature Leydig cells and a growth factor for precursor Leydig cells after ethylene dimethane sulfonate treatment: implication of a role of the stem cell factor/c-Kit system in Leydig cell development. Dev Biol 2000; 227: 169-182. [DOI:10.1006/dbio.2000.9885]
33. Nurmio M. Cancer therapy-related toxicity in the immature testis. [Doctoral thesis]. Turun Yliopiston Julkaisuja: 2009.
34. Turjap M, Jurica J, Demlova R. Potential clinical benefit of therapeutic drug monitoring of imatinib in oncology. Klinicka Onkologie 2015; 28: 105-111. [DOI:10.14735/amko2015105]
35. Al-Hadiya BM, Bakheit AH, Abd-Elgalil AA. Imatinib mesylate. Profiles Drug Subst Excip Relat Methodol 2014; 39: 265-297. [DOI:10.1016/B978-0-12-800173-8.00006-4]
Send email to the article author

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

Designed & Developed by : Yektaweb