5-Azacytidine Enhancing Expression of E-cadherin in Adenocarcinoma Cell Line
Archives of Advances in Biosciences,
Vol. 14 No. 1 (2023),
19 February 2023
,
Page 1-6
https://doi.org/10.22037/aab.v14i1.35171
Abstract
Introduction: In this study, we assessed the expression of E-cadherin in HT29 cell line treated with 5-Azacytidine and colorectal cancer patient in an Iranian population. E-cadherin expression promotes metastasis and prognosis of colorectal cancer (CRC). 5-Azacytidine, a DNA methyl transferase inhibitor, is a clinically used epigenetic drug for treatment of cancer including colorectal cancer, leading to genes activation involved in tumor suppression, especially E-cadherin.
Materials and Methods: HT29 cell line treated with 5-Azacitidine and 40 polyps, 20 tumors and 40 adjacent normal tissues samples were enrolled in this study. Using the real-time PCR method, the expression levels of E-cadherin were examined in treated cell line and colorectal cancer tissue.
Results: This study proves that 5-Azacytidine induces over expression of E-cadherin in adenocarcinoma cell line, while the expression levels of E-cadherin were not different in tumor and polyp than adjacent normal tissue.
Conclusion: To conclude, 5-Azacytidine induces re-expression of E-cadherin in adenocarcinoma cell line. Thus, 5-Azacytidine as demethylation drug activated tumor suppressor gene as E-cadherin.
- Colorectal cancer
- E-cadherin
- Polyps
- 5 Azacytidine
How to Cite
References
. Daraei A, Salehi R, Salehi M, Emami M, Jonghorbani M, Mohamadhashem F, et al. Effect of rs6983267 polymorphism in the 8q24 region and rs4444903 polymorphism in EGF gene on the risk of sporadic colorectal cancer in Iranian population. Med Oncol. 2012;29(2):1044-9. [DOI: 10.1007/s12032-011-9980-2] [PMID]
. Wong MC, Ding H, Wang J, Chan PS, Huang J. Prevalence and risk factors of colorectal cancer in Asia. Intest Res. 2019;17(3):317. [DOI: 10.5217/ir.2019.00021] [PMID] [PMCID]
. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394-424. [DOI: 10.3322/caac.21492] [PMID]
. Sepulveda AR, Hamilton SR, Allegra CJ, Grody W, Cushman-Vokoun AM, Funkhouser WK, et al. Molecular biomarkers for the evaluation of colorectal cancer: guideline from the American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology, and American Society of Clinical Oncology. J Clin Oncol. 2017; 35(13):1453-1486. [DOI: 10.1200/JCO.2016.71.9807] [PMID]
. Noh M-G, Oh S-J, Ahn E-J, Kim Y-J, Jung T-Y, Jung S, et al. Prognostic significance of E-cadherin and N-cadherin expression in Gliomas. BMC cancer. 2017;17(1):583. [DOI: 10.1186/s12885-017-3591-z] [PMID] [PMCID]
. Li Z, Yin S, Zhang L, Liu W, Chen B. Prognostic value of reduced E-cadherin expression in breast cancer: a meta-analysis. Oncotarget. 2017;8(10): 16445-16455. [DOI: 10.18632/oncotarget.14860] [PMID] [PMCID]
. Song Y, Ye M, Zhou J, Wang Z-w, Zhu X. Restoring E-cadherin expression by natural compounds for anticancer therapies in genital and urinary cancers. Mol Ther Oncolytics. 2019;14:130-8. [DOI: 10.1016/j.omto.2019.04.005] [PMID] [PMCID]
. Dong L, Dong Q, Chen Y, Li Y, Zhang B, Zhou F, et al. Novel HDAC5-interacting motifs of Tbx3 are essential for the suppression of E-cadherin expression and for the promotion of metastasis in hepatocellular carcinoma. Sig Transduct Target Ther. 2018;3(1):1-11. [DOI: 10.1038/s41392-018-0025-6]
. Menezes SV, Fouani L, Huang ML, Geleta B, Maleki S, Richardson A, et al. The metastasis suppressor, NDRG1, attenuates oncogenic TGF-β and NF-κB signaling to enhance membrane E-cadherin expression in pancreatic cancer cells. Carcinogenesis. 2019;40(6):805-18. [DOI: 10.1093/carcin/bgy178] [PMID]
. Jalali Nadoushan MR, Taheri T, Jouian N, Zaeri F. Overexpression of HER-2/neu oncogene and transitional cell carcinoma of bladder. Urol J. 2007;4(3):151-4. [PMID]
. Roger L, Jullien L, Gire V, Roux P. Gain of oncogenic function of p53 mutants regulates E-cadherin expression uncoupled from cell invasion in colon cancer cells. J Cell Sci. 2010;123(Pt 8):1295-305. [DOI: 10.1242/jcs.061002] [PMID]
. Paek AR, Lee CH, You HJ. A role of zinc‐finger protein 143 for cancer cell migration and invasion through ZEB1 and E‐cadherin in colon cancer cells. Mol Carcinog. 2014;53(S1):E161-E8. [DOI: 10.1002/mc.22083] [PMID]
. Nagafuchi A, Shirayoshi Y, Okazaki K, Yasuda K, Takeichi M. Transformation of cell adhesion properties by exogenously introduced E-cadherin cDNA. Nature. 1987;329(6137):341-3. [DOI: 10.1038/329341a0] [PMID]
. Gumbiner BM. Regulation of cadherin-mediated adhesion in morphogenesis. Nature reviews Molecular cell biology. 2005;6(8):622-34. [DOI: 10.1038/nrm1699] [PMID]
. Umbas R, Isaacs WB, Bringuier PP, Schaafsma HE, Karthaus HF, Oosterhof GO, et al. Decreased E-cadherin expression is associated with poor prognosis in patients with prostate cancer. Cancer Res. 1994;54(14):3929-33. [PMID]
. Kim SA, Inamura K, Yamauchi M, Nishihara R, Mima K, Sukawa Y, et al. Loss of CDH1 (E-cadherin) expression is associated with infiltrative tumour growth and lymph node metastasis. Br J Cancer. 2016;114(2):199-206. [DOI: 10.1038/bjc.2015.347] [PMID] [PMCID]
. Menke A, Philippi C, Vogelmann R, Seidel B, Lutz MP, Adler G, et al. Down-regulation of E-cadherin gene expression by collagen type I and type III in pancreatic cancer cell lines. Cancer Res. 2001;61(8):3508-17. [PMID]
. Wong SHM, Fang CM, Chuah L-H, Leong CO, Ngai SC. E-cadherin: Its dysregulation in carcinogenesis and clinical implications. Crit Rev Oncol Hematol. 2018;121:11-22. [DOI: 10.1016/j.critrevonc.2017.11.010] [PMID]
. Sajadian SO, Tripura C, Samani FS, Ruoss M, Dooley S, Baharvand H, et al. Vitamin C enhances epigenetic modifications induced by 5-azacytidine and cell cycle arrest in the hepatocellular carcinoma cell lines HLE and Huh7. Clin Epigenetics. 2016;8(1):1-13. [DOI: 10.1186/s13148-016-0213-6] [PMID] [PMCID]
. Ruoß M, Damm G, Vosough M, Ehret L, Grom-Baumgarten C, Petkov M, et al. Epigenetic modifications of the liver tumor cell line HepG2 increase their drug metabolic capacity. International journal of molecular sciences. 2019;20(2):347. [DOI: 10.3390/ijms20020347] [PMID] [PMCID]
. Lu Y, Zhang R, Zhang X, Zhang B, Yao Q. Curcumin may reverse 5-fluorouracil resistance on colonic cancer cells by regulating TET1-NKD-Wnt signal pathway to inhibit the EMT progress. Biomed Pharmacother. 2020;129:110381. [DOI: 10.1016/j.biopha.2020.110381] [PMID]
. Wang Y, Xin L, Chen J, Mei Z, Xie C. Effects of 5-azacytidine on radiation-induced epithelial-mesenchymal transition in rat alveolar type Ⅱ epithelial cell line. Am J Transl Res. 2015;24(3):349-53. [PMID] [PMCID]
. Schneider-Stock R, Diab-Assef M, Rohrbeck A, Foltzer-Jourdainne C, Boltze C, Hartig R, et al. RETRACTION: 5-aza-Cytidine is a potent inhibitor of DNA methyltransferase 3a and induces apoptosis in HCT-116 colon cancer cells via Gadd45-and p53-dependent mechanisms. J Pharmacol Exp Ther. 2005;312(2):525-36. [DOI: 10.1124/jpet.104.074195] [PMID]
. Venturelli S, Berger A, Weiland T, Essmann F, Waibel M, Nuebling T, et al. Differential induction of apoptosis and senescence by the DNA methyltransferase inhibitors 5-azacytidine and 5-aza-2′-deoxycytidine in solid tumor cells. Molecular cancer therapeutics. 2013;12(10):2226-36. [DOI: 10.1158/1535-7163.MCT-13-0137] [PMID]
. Yamanaka S, Campbell NR, An F, Kuo SC, Potter JJ, Mezey E, et al. Coordinated effects of microRNA-494 induce G₂/M arrest in human cholangiocarcinoma. Cell cycle. 2012;11(14):2729-38. [DOI: 10.4161/cc.21105] [PMID] [PMCID]
. Wang X, Chen E, Yang X, Wang Y, Quan Z, Wu X, et al. 5-azacytidine inhibits the proliferation of bladder cancer cells via reversal of the aberrant hypermethylation of the hepaCAM gene. Oncol Rep. 2016;35(3):1375-84. [DOI: 10.3892/or.2015.4492] [PMID]
. Esheba GE, Hassan AA, El Bostany MZ, Aly MH. Prognostic value of cancer stem cell markers and E-cadherin expression in non-small-cell lung cancer. Egyptian Journal of Pathology. 2017;37(2):281-8.
. Wang W, Dong L, Zhao B, Lu J, Zhao Y. E‑cadherin is downregulated by microenvironmental changes in pancreatic cancer and induces EMT. Oncol Rep. 2018;40(3):1641-9. [DOI: 10.3892/or.2018.6528] [PMID]
. Druzhkova I, Ignatova N, Prodanets N, Kiselev N, Zhukov I, Shirmanova M, et al. E-cadherin in colorectal cancer: Relation to chemosensitivity. Clin Colorectal Cancer. 2019;18(1):e74-e86. [DOI: 10.1016/j.clcc.2018.10.003] [PMID]
- Abstract Viewed: 182 times
- PDF Downloaded: 172 times