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Sci J Iran Blood Transfus Organ 2017, 14(4): 314-324 |
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Nikkhoo P, Oodi A, Sotoodehnejadnematalahi F. Effect of harmalin on Dnmt1 expression and hypomethylation of P15 gene promoter in NB4 leukemic cell. Sci J Iran Blood Transfus Organ 2017; 14 (4) :314-324
URL: http://bloodjournal.ir/article-1-1125-en.html
URL: http://bloodjournal.ir/article-1-1125-en.html
Effect of harmalin on Dnmt1 expression and hypomethylation of P15 gene promoter in NB4 leukemic cell
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Effect of harmalin on Dnmt1 expression and
hypomethylation of P15 gene promoter in NB4 leukemic cell
Nikkhoo P.1, Oodi A.1, Sotoodehnejadnematalahi F.2
1Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran
2Department of Biology, School of Basic Science, Islamic Azad University, Tehran, Iran
Abstract
Background and Objectives
One of the most important mechanisms of hematologic malignancies is DNA methylation in the promoter region of tumor suppressor genes such as P15. Harmalin is one of the alkaloids derived from plants that show anti-proliferative activity on leukemic cell lines. The effect of harmalin on Dnmt1 gene expression and hypomethylation of P15 promoter in NB4 cell line was evaluated.
Materials and Methods
In this experimental study, cytotoxic effects of harmaline were investigated until 72 hours on the NB4 cell line using MTT. Flow cytometry was performed in order to evaluate the cell cycle of NB4 cell line after treatment with harmalin. Gene promoter methylation status of P15 was evaluated by Methylation Specific PCR. Dnmt1 and P15 gene expression was analyzed by Real-time PCR technique.
Results
15μg/ml harmalin after 48 hours showed a dose and time-dependent anti-proliferative properties on NB4 cell line, cell cycle analysis would stop NB4 cells in G0G1 phase of the cell cycle. Real-time PCR results showed that 15μg/ml harmalin reduced gene expression of Dnmt1, induced hypomethylation of P15 gene promoter and increased P15 gene expression in NB4 cell line.
Conclusions
According to our data, the effect of harmalin on reduction of Dnmt1 expression, P15 promoter hypomethylation and P15 reactivation in this cell line showed that it could be suggested as a therapeutic strategy, suitable for monotherapy or supplement for medication which is commonly used for APL (Acute Promyeloid Leukemia).
Key words: Methylation, Gene, Leukemia
Received: 13 Jun 2017
Accepted: 20 Aug 2017
Correspondence: Oodi A., PhD of Hematology and Blood Banking. Assistant Professor of Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine.
P.O.Box: 14665-1157, Tehran, Iran. Tel: (+9821) 88601599; Fax : (+9821) 88601599
E-mail: ar.oody@gmail.com
Full-Text: (4015 Views)
References:
- Herceg Z, Hainaut P. Genetic and epigenetic alterations as biomarkers for cancer detection, diagnosis and prognosis. Mol Oncol 2007; 1(1): 26-41.
- Borutinskaite V, Bauraite-Akatova J, Navakauskiene R. Anti-leukemic activity of DNA methyltransferase inhibitor procaine targeted on human leukaemia cells. Open Life Sciences 2016; 11(1): 322-30.
- De Braekeleer M, Douet-Guilbert N, De Braekeleer E.
- Bodoor K, Haddad Y, Alkhateeb A, Al-Abbadi A, Dowairi M, Magableh A, et al. DNA hypermethylation of cell cycle (p15 and p16) and apoptotic (p14, p53, DAPK and TMS1) genes in peripheral blood of leukemia patients. Asian Pac J Cancer Prev 2014; 15(1): 75-84.
- Ren J, Singh BN, Huang Q, Li Z, Gao Y, Mishra P, et al. DNA hypermethylation as a chemotherapy target. Cell Signal 2011; 23(7): 1082-93.
- Amirizadeh N, Oodi A, Nikougoftar M, Soltanpour
- Zaker F, Oody A, Arjmand A. A study on the antitumoral and differentiation effects of Peganum harmala derivatives in combination with ATRA on leukaemic cells. Arch Pharm Res 2007; 30(7): 844-9.
- Oodi A, Norouzi H, Amirizadeh N, Nikougoftar M, Vafaie Z. Harmine, a Novel DNA Methyltransferase 1 Inhibitor in the Leukemia Cell Line. Indian J Hematol Blood Transfus 2017; 33(4): 509-15.
- Forouzandeh F, Salimi S, Naghsh N, Zamani N, Jahani S. Evaluation of anti-cancer effect of Peganum harmala L hydroalcholic extract on human cervical carcinoma epithelial cell line. J Shahrekord Univ Med Sci 2014; 16(4): 1-8. [Article in Farsi]
- Blum W, Marcucci G. Targeting epigenetic changes in acute myeloid leukemia. Clinical advances in hematology & oncology: H&O 2005; 3(11): 855-65, 82.
- Montesano A, Luzi L, Senesi P, Terruzzi I. Modulation of cell cycle progression by 5-azacytidine is associated
with early myogenesis induction in murine myoblasts. Int J Biol Sci 2013; 9(4): 391-402. - Hamsa TP, Kuttan G. Harmine activates intrinsic and extrinsic pathways of apoptosis in B16F-10 melanoma. Chin Med 2011; 6(1): 11.
- Yu J, Peng Y, Wu LC, Xie Z, Deng Y, Hughes T, et al. Curcumin down-regulates DNA methyltransferase 1 and plays an anti-leukemic role in acute myeloid leukemia. PLoS One 2013; 8(2): e55934.
- Hassan HE, Carlson S, Abdallah I, Buttolph T, Glass KC, Fandy TE. Curcumin and dimethoxycurcumin induced epigenetic changes in leukemia cells. Pharm Res 2015; 32(3): 863-75.
- Achour M, Mousli M, Alhosin M, Ibrahim A, Peluso J, Muller CD, et al. Epigallocatechin-3-gallate up-regulates tumor suppressor gene expression via a reactive oxygen species-dependent down-regulation of UHRF1. Biochem Biophys Res Commun 2013; 430(1): 208-12.
- Agarwal S, Amin KS, Jagadeesh S, Baishay G, Rao PG, Barua NC, et al. Mahanine restores RASSF1A expression by down-regulating DNMT1 and DNMT3B in prostate cancer cells. Mol Cancer 2013; 12(1): 99.
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Sci J Iran Blood Transfus Organ 2018; 14(4): 314-324 |
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Original Article
|
Effect of harmalin on Dnmt1 expression and
hypomethylation of P15 gene promoter in NB4 leukemic cell
Nikkhoo P.1, Oodi A.1, Sotoodehnejadnematalahi F.2
1Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran
2Department of Biology, School of Basic Science, Islamic Azad University, Tehran, Iran
Abstract
Background and Objectives
One of the most important mechanisms of hematologic malignancies is DNA methylation in the promoter region of tumor suppressor genes such as P15. Harmalin is one of the alkaloids derived from plants that show anti-proliferative activity on leukemic cell lines. The effect of harmalin on Dnmt1 gene expression and hypomethylation of P15 promoter in NB4 cell line was evaluated.
Materials and Methods
In this experimental study, cytotoxic effects of harmaline were investigated until 72 hours on the NB4 cell line using MTT. Flow cytometry was performed in order to evaluate the cell cycle of NB4 cell line after treatment with harmalin. Gene promoter methylation status of P15 was evaluated by Methylation Specific PCR. Dnmt1 and P15 gene expression was analyzed by Real-time PCR technique.
Results
15μg/ml harmalin after 48 hours showed a dose and time-dependent anti-proliferative properties on NB4 cell line, cell cycle analysis would stop NB4 cells in G0G1 phase of the cell cycle. Real-time PCR results showed that 15μg/ml harmalin reduced gene expression of Dnmt1, induced hypomethylation of P15 gene promoter and increased P15 gene expression in NB4 cell line.
Conclusions
According to our data, the effect of harmalin on reduction of Dnmt1 expression, P15 promoter hypomethylation and P15 reactivation in this cell line showed that it could be suggested as a therapeutic strategy, suitable for monotherapy or supplement for medication which is commonly used for APL (Acute Promyeloid Leukemia).
Key words: Methylation, Gene, Leukemia
Received: 13 Jun 2017
Accepted: 20 Aug 2017
Correspondence: Oodi A., PhD of Hematology and Blood Banking. Assistant Professor of Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine.
P.O.Box: 14665-1157, Tehran, Iran. Tel: (+9821) 88601599; Fax : (+9821) 88601599
E-mail: ar.oody@gmail.com
Send email to the article author
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