Investigation of the Effect of Zebularine in Comparison to and in Combination with Trichostatin A on P21Cip1/Waf1/ Sdi1, P27Kip1, P57Kip2, DNA Methyltransferases and Histone Deacetylases in Colon Cancer LS 180 Cell Line

Overview

Journal Asian Pac J Cancer Prev

Specialty Oncology

Date 2020 Jun 28

PMID 32592383

Citations 8

Authors

Masumeh Sanaei

Fraidoon Kavoosi

Affiliations

Soon will be listed here.

Abstract

Background: The heart of the cell cycle regulatory machine is a group of enzymes named cyclin-dependent kinases (Cdks). The active form of these enzymes includes a kinase and its partner, a cyclin. The regulation of cyclin-Cdk complexes is provided by Cdk inhibitors (CKIs) such as Cip/Kip family comprising p21Cip1/Waf1/Sdi1, p27Kip1, and p57Kip2. The hypermethylation and deacetylation of Cip/Kip gene family seem to be frequent in numerous cancers. It has been indicated that increased expression of DNMTs and HDACs contributes to cancer induction. Previously, we reported the effect of DNA demethylating agents and histone deacetylase inhibitors on histone deacetylase 1, DNA methyltransferase 1, and CIP/KIP family in colon cancer. The current study was designed to evaluate the effect of zebularine in comparison to and in combination with trichostatin A (TSA) on p21Cip1/Waf1/Sdi1, p27Kip1, p57Kip2, DNA methyltransferases (DNMT1, 3a and 3b) and histone deacetylases (HDAC1, 2, and 3) genes expression, cell growth inhibition and apoptosis induction in colon cancer LS 180 cell line.

Materials And Methods: The colon cancer LS 180 cell line was cultured and treated with zebularine and TSA. To determine cell viability, apoptosis, and the relative expression level of the genes, MTT assay, cell apoptosis assay, and qRT-PCR were done respectively.

Results: Both compounds significantly inhibited cell growth, and induced apoptosis. Furthermore, both compounds increased p21Cip1/Waf1/Sdi1, p27Kip1, and p57Kip2 significantly. Additionally, zebularine and TSA decreased DNMTs and HDACs gene expression respectively.

Conclusion: The zebularine and TSA can reactivate the CIP/KIP family through inhibition of DNMTs and HDACs genes activity.<br />.

Citing Articles

Effect of Zebularine on Apoptotic Pathways in Hepatocellular Carcinoma Cell Lines.

Sanaei M, Kavoosi F Int J Prev Med. 2023; 14:63.

PMID: 37351028 PMC: 10284256. DOI: 10.4103/ijpvm.ijpvm_191_21.

Effect of 5'-Fluoro-2'-Deoxycytidine and Sodium Butyrate on the Gene Expression of the Intrinsic Apoptotic Pathway, p21, p27, and p53 Genes Expression, Cell Viability, and Apoptosis in Human Hepatocellular Carcinoma Cell Lines.

Sanaei M, Kavoosi F, Safari M Adv Biomed Res. 2023; 12:24.

PMID: 37057236 PMC: 10086643. DOI: 10.4103/abr.abr_211_21.

Multimodal Imaging under Artificial Intelligence Algorithm for the Diagnosis of Liver Cancer and Its Relationship with Expressions of EZH2 and p57.

Zhang Y, Cui J, Wan W, Liu J Comput Intell Neurosci. 2022; 2022:4081654.

PMID: 35321452 PMC: 8938086. DOI: 10.1155/2022/4081654.

Histone Deacetylase Inhibitors, Intrinsic and Extrinsic Apoptotic Pathways, and Epigenetic Alterations of Histone Deacetylases (HDACs) in Hepatocellular Carcinoma.

Sanaei M, Kavoosi F Iran J Pharm Res. 2021; 20(3):324-336.

PMID: 34903992 PMC: 8653641. DOI: 10.22037/ijpr.2021.115105.15197.

Effect of Zebularine in Comparison to Trichostatin A on the Intrinsic and Extrinsic Apoptotic Pathway, Cell Viability, and Apoptosis in Hepatocellular Carcinoma SK-Hep 1, Human Colorectal Cancer SW620, and Human Pancreatic Cancer PaCa-44 Cell Lines.

Sanaei M, Kavoosi F Iran J Pharm Res. 2021; 20(3):310-323.

PMID: 34903991 PMC: 8653687. DOI: 10.22037/ijpr.2021.115097.15196.

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