title: Aberrant epigenetic alteration in Eca9706 cells modulated by nanoliposomal quercetin combined with butyrate mediated via epigenetic-NF-κB signaling.
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-κBp65, HDAC1 and Cyclin D1 were down-regulated, while expressions of caspase-3 and p16INK4α 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 p16INK4α: 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-κB cascade signaling.
authors: Department of Basic Sci of Oncology, Medical College of Zhengzhou University, Zhengzhou, China E-mail : zhengng@zzu.edu.cn.
authors: Nai-Gang
authors: NG
authors: Zheng
authors: Jun-Ling
authors: JL
authors: Wang
authors: Sheng-Li
authors: SL
authors: Yang
authors: Jing-Lan
authors: JL
authors: Wu
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D002087:Butyrates / Q000008:administration & dosage; D015820:Cadherins / Q000235:genetics; D053148:Caspase 3 / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D019938:Cyclin D1 / Q000235:genetics; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics; D019175:DNA Methylation / Q000187:drug effects / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D044127:Epigenesis, Genetic / Q000187:drug effects* / Q000235:genetics*; D056284:Histone Deacetylase 1 / Q000235:genetics; D006801:Humans; D008081:Liposomes / Q000008:administration & dosage; D016328:NF-kappa B / Q000235:genetics*; D053758:Nanoparticles / Q000008:administration & dosage; D011794:Quercetin / Q000008:administration & dosage; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D002087:Butyrates; D015820:Cadherins; D008081:Liposomes; D016328:NF-kappa B; D019938:Cyclin D1; D011794:Quercetin; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human; D053148:Caspase 3; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1