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
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 kin...
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doaj-3fe024b4d740432ebd3c47335146e8df2021-07-27T04:31:48ZengWolters Kluwer Medknow PublicationsInternational Journal of Preventive Medicine2008-78022008-82132021-01-01121646410.4103/ijpvm.IJPVM_11_20Investigation 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 lineMasumeh SanaeiFraidoon KavoosiVahid GhasemzadehBackground: 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.http://www.ijpvmjournal.net/article.asp?issn=2008-7802;year=2021;volume=12;issue=1;spage=64;epage=64;aulast=Sanaeicolonic neoplasmscyclin-dependent kinase inhibitorsdecitabinetrichostatin a |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Masumeh Sanaei Fraidoon Kavoosi Vahid Ghasemzadeh |
spellingShingle |
Masumeh Sanaei Fraidoon Kavoosi Vahid Ghasemzadeh 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 International Journal of Preventive Medicine colonic neoplasms cyclin-dependent kinase inhibitors decitabine trichostatin a |
author_facet |
Masumeh Sanaei Fraidoon Kavoosi Vahid Ghasemzadeh |
author_sort |
Masumeh Sanaei |
title |
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 |
title_short |
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 |
title_full |
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 |
title_fullStr |
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 |
title_full_unstemmed |
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 |
title_sort |
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 |
publisher |
Wolters Kluwer Medknow Publications |
series |
International Journal of Preventive Medicine |
issn |
2008-7802 2008-8213 |
publishDate |
2021-01-01 |
description |
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. |
topic |
colonic neoplasms cyclin-dependent kinase inhibitors decitabine trichostatin a |
url |
http://www.ijpvmjournal.net/article.asp?issn=2008-7802;year=2021;volume=12;issue=1;spage=64;epage=64;aulast=Sanaei |
work_keys_str_mv |
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