| ORIGINAL ARTICLE |
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| Year : 2021 | Volume
: 12
| Issue : 1 | Page : 64 |
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Investigation of the effect of 5-Aza-2'-deoxycytidine in comparison to and in combination with trichostatin a on p16INK4a, p14ARF, p15INK4b gene expression, cell growth inhibition and apoptosis induction in colon cancer Caco-2 cell line
Masumeh Sanaei1, Fraidoon Kavoosi1, Vahid Ghasemzadeh2
1 Research Center for Non-Communicable Diseases, Jahrom University of Medical Sciences, Jahrom, Fars Province, Iran
2 Department of Student of Research Committee, Jahrom University of Medical Sciences, Jahrom, Fars Province, Iran
Correspondence Address:
Fraidoon Kavoosi
Research Center for Non-Communicable Diseases, Jahrom University of Medical Sciences, Jahrom - 74148-46199, Fars Province
Iran
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/ijpvm.IJPVM_11_20
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Background: The cell cycle is divided into four phases, G1, G2, S, and M phase. The mammalian cell cycle is controlled and governed by the kinase complexes including cyclin and the cyclin-dependent kinase (CDK), cyclin-CDK complexes. The activity of the complexes is regulated by cyclin-dependent kinase inhibitors (CDKIs), the INK4, and the CDK interacting protein/kinase inhibitory protein (CIP/KIP) families. Promoter hypermethylation and histone deacetylation of CDKIs have been reported in several cancers. These changes can be reversed by DNA demethylating agents, such as decitabine, 5-Aza-2′-deoxycytidine (5-Aza-CdR), and histone deacetylase inhibitors (HDACIs), such as trichostatin A. Previously, we reported the effect of 5-Aza-CdR and trichostatin A (TSA) on hepatocellular carcinoma (HCC). The present study aimed to investigate the effect of 5-Aza-CdR in comparison to and in combination with trichostatin A on p16INK4a, p14ARF, p15INK4b genes expression, cell growth inhibition and apoptosis induction in colon cancer Caco-2 cell line. Methods: The Caco-2 cells were cultured and treated with 5-Aza-CdR and TSA (alone and combined). The cell viability, apoptosis, and relative gene expression were determined by MTT assay, flow cytometry, and real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR), respectively. Results: Both compounds inhibited cell growth, induced apoptosis, and up-regulated the p16INK4a, p14ARF, p15INK4b gene significantly. The TSA had a more significant effect in comparison to 5-Aza-CdR. Furthermore, maximal apoptosis and up-regulation were observed with combined treatment. Conclusions: our finding indicated that 5-Aza-CdR and TSA can epigenetically re-activate the p16INK4a, p14ARF, p15INK4b gene resulting in cell growth inhibition and apoptosis induction in colon cancer.
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