Volume 25, Issue 8 (Oct 2017)
JSSU 2017, 25(8): 670-680 |
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Dadakhani S, Pazhang Y, Imani M. Anti-proliferative Effects of Hydralazine on K562 Cell Line (CML). JSSU 2017; 25 (8) :670-680
URL: http://jssu.ssu.ac.ir/article-1-4166-en.html
URL: http://jssu.ssu.ac.ir/article-1-4166-en.html
Abstract: (4651 Views)
Introduction: Cancer is the second leading cause of death in the world and among the types of cancer, leukemia is one of the deadliest. Chronic myeloid leukemia (CML) is the best known types of leukemia. Hydralazine is in the cardiovascular medical group, which is considering as inhibitory factor on the proliferation of cancer cells by knowing its inhibitory effects on DNA methyltransferase. The purpose of this study was to evaluate the inhibitory effects of hydralazine on K562 cells proliferation.
Methods: First, the K562 cells were cultured. After, the different concentrations of the hydralazine were prepared and the cells were treated for 24, 48 and 72 hours. Next, the inhibitory effects of this drug on K562 cells proliferation was measured by MTT assay. Hoechst (33342) staining and DNA electrophoresis was used to check apoptosis. Data analyses were performed using SPSS software (Version 20) and ANOVA test (P<0.05).
Results: MTT assay results showed that hydralazine has the highest cytotoxic activity in 80μM at 72 hours. Drug IC50 was obtained 81 micromolar. And also the results of Hoechst staining and DNA electrophoresis showed that hydralazine was caused apoptosis.
Conclusion: In the present study, it was shown that hydralazine induces cells death by apoptosis and this effect was dose-dependent and treat time dependent. It is suggested that more studies will be done on the effects of this drug on animal models and human.
Methods: First, the K562 cells were cultured. After, the different concentrations of the hydralazine were prepared and the cells were treated for 24, 48 and 72 hours. Next, the inhibitory effects of this drug on K562 cells proliferation was measured by MTT assay. Hoechst (33342) staining and DNA electrophoresis was used to check apoptosis. Data analyses were performed using SPSS software (Version 20) and ANOVA test (P<0.05).
Results: MTT assay results showed that hydralazine has the highest cytotoxic activity in 80μM at 72 hours. Drug IC50 was obtained 81 micromolar. And also the results of Hoechst staining and DNA electrophoresis showed that hydralazine was caused apoptosis.
Conclusion: In the present study, it was shown that hydralazine induces cells death by apoptosis and this effect was dose-dependent and treat time dependent. It is suggested that more studies will be done on the effects of this drug on animal models and human.
Type of Study: Original article |
Subject:
Biochemistry
Received: 2017/04/17 | Accepted: 2017/07/29 | Published: 2017/12/5
Received: 2017/04/17 | Accepted: 2017/07/29 | Published: 2017/12/5
References
2. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. International j cancer 2010; 127(12): 2893-917.
3. Swapnil K, Vijay S, Chandrakant M. Targeted Drug Delivery: A Backbone for Cancer Therapy. Asian J Pharmacy and Technology 2013; 3(1): 40-6.
4. Garrett MD. Cell cycle control and cancer. CURRENT SCIENCE-BANGALORE- 2001; 81(5): 515-22.
5. Balunas MJ, Kinghorn AD. Drug discovery from medicinal plants. Life sciences 2005; 78(5): 431-41.
6. Parkin DM. Global cancer statistics in the year 2000. The lancet oncology 2001; 2(9): 533-43.
7. Işikdağ İ, Özkay Y, İncesu Z. Synthesis and anticancer activity of some bisquinoxaline derivatives. Turk J. Pharm. Sci 2011; 8(2): 179-88.
8. Mossoomy Z, Mesgari M. Detection of leukemia epidemiology in Iran using GIS and statistical analyses. Pediatric Hematology and Oncology 2008; 32: 441-8.
9. Delluc S, Tourneur L, Michallet AS, Boix C, Varet B, Fradelizi D, et al. Autologous peptides eluted from acute myeloid leukemia cells can be used to generate specific antileukemic CD4 helper and CD8 cytotoxic T lymphocyte responses in vitro. Haematologica 2005; 90(8): 1050-62.
10. Roussel MJ, Lanotte M. Maturation sensitive and resistant t (15; 17) NB4 cell lines as tools for APL physiopathology: nomenclature of cells and repertory of their known genetic alterations and phenotypes. Oncogene 2001; 20(49): 7287.
11. Dai Z, Quackenbush RC, Courtney KD, Grove M, Cortez D, Reuther GW, et al. Oncogenic Abl and Src tyrosine kinases elicit the ubiquitin-dependent degradation of target proteins through a Ras-independent pathway. Genes & development 1998; 12(10): 1415-24.
12. Clarkson B, Strife A, Wisniewski D, Lambek CL, Liu C. Chronic myelogenous leukemia as a paradigm of early cancer and possible curative strategies. Leukemia 2003; 17(7): 1211-62.
13. Catherine M, Verfaillie R, Scott M, Robert C.H. Gene therapy for chronic myelogenous leukemia..molecular med today 1999; 5(8): 359-66.
14. Melo JV. 2 BCR-ABL gene variants. Baillière's clinical haematology 1997; 10(2): 203-22.
15. Koeffler HP, Golde DW. Human myeloid leukemia cell lines: a review. Blood 1980; 56(3): 344-50.
16. Esteller M. Epigenetics in cancer. New England Journal of Medicine 2008; 358(11): 1148-59.
17. Lande-Diner L, Cedar H. Silence of the genes—mechanisms of long-term repression. Nature Reviews Genetics 2005; 6(8): 648-54.
18. Lyko F, Brown R. DNA methyltransferase inhibitors and the development of epigenetic cancer therapies. J the National Cancer Institute 2005; 97(20): 1498-506.
19. Barski A, Cuddapah S, Cui K, Roh TY, Schones DE, Wang Z, et al. High-resolution profiling of histone methylations in the human genome. Cell 2007; 129(4): 823-37.
20. Song Y, Zhang C. Hydralazine inhibits human cervical cancer cell growth in vitro in association with APC demethylation and re-expression. Cancer chemotherapy and pharmacology 2009; 63(4): 605-13.
21. Chavez-Blanco A, Perez-Plasencia C, Perez-Cardenas E, Carrasco-Legleu C, Rangel-Lopez E, Segura-Pacheco B, Taja-Chayeb L, et al. Antineoplastic effects of the DNA methylation inhibitor hydralazine and the histone deacetylase inhibitor valproic acid in cancer cell lines. Cancer cell international 2006; 6(1): 2.
22. Xu MH, Zhang GY. Effect of indomethacin on cell cycle proteins in colon cancer cell lines. World J Gastroenterology: WJG 2005; 11(11): 1693-6.
23. Mahdavi M, Davoodi J, Zali MR, Foroumadi A. Concomitant activation of caspase-9 and down-regulation of IAP proteins as a mechanism of apoptotic death in HepG2, T47D and HCT-116 cells upon exposure to a derivative from 4-aryl-4H-chromenes family. Biomedicine & Pharmacotherapy 2011; 65(3): 175-82.
24. Bellosillo B, Piqué M, Barragán M, Castaño E, Villamor N, Colomer D, et al. Aspirin and salicylate induce apoptosis and activation of caspases in B-cell chronic lymphocytic leukemia cells. Blood 1998; 92(4): 1406-14.
25. Allen S, Sotos J, Sylte MJ, Czuprynski CJ. Use of Hoechst 33342 staining to detect apoptotic changes in bovine mononuclear phagocytes infected with Mycobacterium avium subsp. paratuberculosis. Clinical and diagnostic laboratory immunology 2001; 8(2):460-4.
26. Singh N, Dueñas‐González A, Lyko F, Medina‐Franco JL. Molecular modeling and molecular dynamics studies of hydralazine with human DNA methyltransferase 1. ChemMedChem 2009; 4(5): 792-9.
27. Davis CD, Uthus EO. DNA methylation, cancer susceptibility, and nutrient interactions. Experimental biology and med 2004; 229(10): 988-95.
28. Segura-Pacheco B, Perez-Cardenas E, Taja-Chayeb L, Chavez-Blanco A, Revilla-Vazquez A, Benitez-Bribiesca L, et al. Global DNA hypermethylation-associated cancer chemotherapy resistance and its reversion with the demethylating agent hydralazine. J translational med 2006; 4(1): 32
29. Zambrano P, Segura-Pacheco B, Perez-Cardenas E, Cetina L, Revilla-Vazquez A, Taja-Chayeb L, et al. A phase I study of hydralazine to demethylate and reactivate the expression of tumor suppressor genes. BMC cancer 2005; 5(1): 44.
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