DOI QR코드

DOI QR Code

Aberrant Epigenetic Alteration in Eca9706 Cells Modulated by Nanoliposomal Quercetin Combined with Butyrate Mediated via Epigenetic-NF-κB Signaling

  • Zheng, Nai-Gang (Department of Basic Sci of Oncology, Medical College of Zhengzhou University) ;
  • Wang, Jun-Ling (Department of Basic Sci of Oncology, Medical College of Zhengzhou University) ;
  • Yang, Sheng-Li (Department of Basic Sci of Oncology, Medical College of Zhengzhou University) ;
  • Wu, Jing-Lan (Molecular Cell Biology Research Center, Medical College of Zhengzhou University)
  • Published : 2014.06.15

Abstract

Since the epigenetic alteration in tumor cells can be reversed by the dietary polyphenol quercetin (Q) or butyrate (B) with chemopreventive activity, suggesting that Q or B can be used for chemopreventive as well as therapeutic agent against tumors. In this study the polyphenol flavonoid quercetin (Q) or sodium butyrate (B) suppressed human esophageal 9706 cancer cell growth in dose dependent manner, and Q combined with B (Q+B) could further inhibit Eca9706 cell proliferation than that induced by Q or B alone, compared with untreated control group (C) in MTT assay. The reverse expressions of global DNMT1, $NF-{\kappa}Bp65$, HDAC1 and Cyclin D1 were down-regulated, while expressions of caspase-3 and $p16INK4{\alpha}$ were up-regulated, compared with the C group in immunoblotting; the down-regulated HDAC1-IR (-immunoreactivity) with nuclear translocation, and up-regulated E-cadherin-IR demonstrated in immunocytochemistry treated by Q or B, and Q+B also displayed further negatively and positively modulated effects compared with C group. The order of methylation specific (MS) PCR of $p16INK4{\alpha}$: C>B/Q>Q+B group, while the order of E-cadherin expression level was contrary, Q+B>Q/B>C group. Thus, Q/B, especially Q+B display reverse effect targeting both altered DNA methylation and histone acetylation, acting as histone deacetylase inhibitor mediated via epigenetic-$NF-{\kappa}B$ cascade signaling.

References

  1. de Corti A, Tryndyak V, Koturbush I, et al (2013). The chemopreventive activity of the butyric acid prodrug tributyrin in experimental rat hepatocarcinogenesis is associated with p53 acetylation and activation of the p53 apoptotic signaling pathway. Carcinogenesis, (Epub ahead of print).
  2. Abizadeh E, Bairey O, Aviram A, et al (2001). Doxrubincin and a butyric acid derivative effectively reduce levels of BCL-2 protein in the cells of chronic lymphocytic leukemia patient. Eur J Haematol, 66, 263-71. https://doi.org/10.1034/j.1600-0609.2001.066004263.x
  3. Chen J, kang JH (2005). Quercetin and trichostatin A cooperatively kill human leukemia cells. Pharmazie 60, 856-60.
  4. Condorelli FI, Gnemmi I, Vallario A, et al (2008). Inhibitors of histone deacetylase (HDAC) restore the p53 pathway in neuroblastoma cells. Br J Pharmacol, 53, 657-68.
  5. Donnelly LE, Newton R, Kennedy GE, et al (2004). Anti-inflammatory effects of resveratrol in lung epithelial cells, molecular mechanisms. Am J Physiol Lung Cell Mol Physiol, 287, L774-83 https://doi.org/10.1152/ajplung.00110.2004
  6. Gerhauser C, Klimo K, Heiss E, et al (2003). Mechanism-based in vitro screening of potential cancer chemopreventive agents. Mutat Res, 523, 163-72.
  7. Gupta SC, Kim J.H, Kannappan R, et al (2011). Role of nuclear factor ${\kappa}B$-mediated inflammatory pathways in cancer-related symptoms and their regulation by nutritional agents. Exp Biol Med, 236, 658-71. https://doi.org/10.1258/ebm.2011.011028
  8. .Indap MA, Barkume MS (2003). Efficacies of plant phonolic compounds on sodium butyrate induced anti-tumour activity. India J Exp Biol, 41, 861-4.
  9. Jun H. Lee, Anjan Nan (2012). Combination drug delivery approaches in metastatic breast cancer. J Drug Delivery, 2012.
  10. Kang TB, Liang NC (1997). Effect on quercetin on activities of protein kinase C and tyrosine protein kinase from HL60 cells. Zhong Gon Yao Li Xue Bao, 18, 374-6
  11. Link A, Balaguer F, Goel A (2010). Cancer chemoprevention by dietary polyphenols, Promosing role for epigenetics. Biochem Pharmacol, 80, 1771-92. https://doi.org/10.1016/j.bcp.2010.06.036
  12. Kihslinger JE, Godley LA (2007). The use of hypomethylating agents in the treatment of hematologic malignancies. Leuk Lymphoma, 48, 1576-95.
  13. Lehmann A, Denkert C, Budczies J et al (2009). High class I HDAC activity and expression are associated with RelA/p65 activation in pancreatic cancer in vitro and in vivo. BMC Cancer, 9, 395. https://doi.org/10.1186/1471-2407-9-395
  14. Lei W, Zhang K, Pan X, et al (2010). Histone deacetylase 1 is required for transforming growth factor-beta 1- induced epithelial-mesenchymal transition. Int J Biochem Cell Biol. 42, 1489-97. https://doi.org/10.1016/j.biocel.2010.05.006
  15. Miki Y, Mukae S, Murakami M, et al (2007). Butyrate inhibits oral cancer cell proliferation and regulates expression of secretory phospholipase A2-X and COX-2. Anticancer Res, 27, 1493-502.
  16. Pan MH, Lai CS, Dushenkov S, Ho CT (2009). Modulation of inflammatory genes by natural dietary bioactive compounds. J Agric Food Chem, 57, 4467-77. https://doi.org/10.1021/jf900612n
  17. Pandurangan AKI, Periasamy S, Anandasadagopan Sk, et al (2012). Green tea polyphenol protection against 4-nitroqinoline 1-oxide-induced bone marrow lipid peroxidation and genotoxicity in Wistar rats. Asian Pac J Cancer Prev, 13, 4107-12. https://doi.org/10.7314/APJCP.2012.13.8.4107
  18. Park MH, Choi MS, Kwak DH, et al (2011). Anti-cancer effect of bee venom in prostate cancer cells through activation of caspase pathway via inactivation of NF-${\kappa}B$. Prostate, 71, 801-12. https://doi.org/10.1002/pros.21296
  19. Pfeuffer M (2013). Effect of quercetin on traits of the metabolic syndrome, endothelial function and inflammation in men with different APOE isoforms in nutrition. Metabolism and Cardiovascular Diseases, 23, 403-9. https://doi.org/10.1016/j.numecd.2011.08.010
  20. Tan S, Wang C, Lu C, et al (2009). Quercetin is able to demethylate the p16INK4$\alpha$ gene promoter. Chemotherapy, 55, 6-10. https://doi.org/10.1159/000166383
  21. Prasad S, Phromnoi K, Yadav VR, et al (2010) Targeting inflammatory pathways by flanonoids for prevention and treatment of cancer. Planta Med, 76, 1044-63. https://doi.org/10.1055/s-0030-1250111
  22. Steliou K, Boosalis MS, Perrine SP, et al (2012). Butyrate histone deacetylase inhibitors. Biores Open Access, 1, 192-8. https://doi.org/10.1089/biores.2012.0223
  23. Strippoli B, Benedicoto I, Foronda M. et al (2010). P38 maintains E-cadherin in expression by modulating TAK1-NF- (kappa) B during epithelial to-mensenchymal transition. J Cell Sci, 123, 4321-31. https://doi.org/10.1242/jcs.071647
  24. Tunon MJ, Garcia-Mediavilla MV, Sanchez-Campos S, Gonzalez-Gallego J. (2009). Potential of flavonoids as anti-inflammatory agents, modulation of pro-inflammatory gene expression and signal transduction pathways. Cur Drug Metab, 10, 256-71. https://doi.org/10.2174/138920009787846369
  25. Wilczynski J, Duechler M, Czyz M (2011). Targeting NF-${\kappa}B$ and HIF-1 pathways for the treatment of cancer, part 1. Arch Immunol Ther Exp (Warsz), 59, 289-99. https://doi.org/10.1007/s00005-011-0131-4
  26. Zhang YI, Zhao L, Bao YL, et al (2010). Butyrate induces apoptosis through activation of JNK MAP kinase pathway in human colon cancer RKO cells. Chem Biol Interact, 185, 174-81. https://doi.org/10.1016/j.cbi.2010.03.035
  27. Zhang QX, Zheng NG, Zhang Y, et al (2007). Redox-evolution of Eca-109 cells by 8-Br-cAMP or quercetin and correlation with p16 ssDNA binding nuclear matrix protein. Life Sci J, 4, 1-7.
  28. Zheng FJI, Shi L, Yang J, et al (2012). Effect of tea polyphenols on the adhesion on highly metastatic human lung carcinoma cell lines to endothelial cells in vitro. Asian Pac J Cancer Prev, 13, 3751-5. https://doi.org/10.7314/APJCP.2012.13.8.3751

Cited by

  1. Clinical Observation and Therapeutic Evaluation of Rh-endostatin Combined with DP Regimen in Treating Patients with Advanced Esophageal Cancer vol.15, pp.16, 2014, https://doi.org/10.7314/APJCP.2014.15.16.6565
  2. An overview of epigenetics in Chinese medicine researches vol.23, pp.9, 2017, https://doi.org/10.1007/s11655-016-2274-y