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Title: Molecular mechanisms for inhibition of colon cancer cells by combined epigenetic-modulating epigallocatechin gallate and sodium butyrate

Abstract

Bioactive compounds are considered safe and have been shown to alter genetic and epigenetic profiles of tumor cells. However, many of these changes have been reported at molecular concentrations higher than physiologically achievable levels. We investigated the role of the combinatorial effects of epigallocatechin gallate (EGCG), a predominant polyphenol in green tea, and sodium butyrate (NaB), a dietary microbial fermentation product of fiber, in the regulation of survivin, which is an overexpressed anti-apoptotic protein in colon cancer cells. For the first time, our study showed that the combination treatment induced apoptosis and cell cycle arrest in RKO, HCT-116 and HT-29 colorectal cancer cells. This was found to be regulated by the decrease in HDAC1, DNMT1, survivin and HDAC activity in all three cell lines. A G2/M arrest was observed for RKO and HCT-116 cells, and G1 arrest for HT-29 colorectal cancer cells for combinatorial treatment. Further experimentation of the molecular mechanisms in RKO colorectal cancer (CRC) cells revealed a p53-dependent induction of p21 and an increase in nuclear factor kappa B (NF-κB)-p65. An increase in double strand breaks as determined by gamma-H2A histone family member X (γ-H2AX) protein levels and induction of histone H3 hyperacetylation was also observed with themore » combination treatment. Further, we observed a decrease in global CpG methylation. Taken together, these findings suggest that at low and physiologically achievable concentrations, combinatorial EGCG and NaB are effective in promoting apoptosis, inducing cell cycle arrest and DNA-damage in CRC cells. - Highlights: • EGCG and NaB as a combination inhibits colorectal cancer cell proliferation. • The combination treatment induces DNA damage, G2/M and G1 arrest and apoptosis. • Survivin is effectively down-regulated by the combination treatment. • p21 and p53 expressions are induced by the combination treatment. • Epigenetic proteins DNMT1 and HDAC1 are effectively down-regulated by the treatment.« less

Authors:
 [1]
  1. Department of Biology, University of Alabama at Birmingham, 175 Campbell Hall, 1300 University Boulevard, Birmingham, AL 35294 (United States)
Publication Date:
OSTI Identifier:
22395897
Resource Type:
Journal Article
Journal Name:
Experimental Cell Research
Additional Journal Information:
Journal Volume: 324; Journal Issue: 1; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0014-4827
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; APOPTOSIS; CELL CYCLE; CELL PROLIFERATION; CHROMATIN; CONCENTRATION RATIO; DMSO; DNA; ECOLOGICAL CONCENTRATION; IODIDES; LARGE INTESTINE; METHYL TRANSFERASES; METHYLATION; NEOPLASMS; POLYMERASE CHAIN REACTION; SODIUM; STRAND BREAKS

Citation Formats

Saldanha, Sabita N., E-mail: sabivan@uab.edu, Department of Biological Sciences, Alabama State University, Montgomery, AL 36104, Kala, Rishabh, Tollefsbol, Trygve O., E-mail: trygve@uab.edu, Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35294, Comprehensive Center for Healthy Aging, University of Alabama at Birmingham, Birmingham, AL 35294, Nutrition Obesity Research Center, University of Alabama at Birmingham, Birmingham, AL 35294, and Comprehensive Diabetes Research Center, University of Alabama at Birmingham, Birmingham, AL 35294. Molecular mechanisms for inhibition of colon cancer cells by combined epigenetic-modulating epigallocatechin gallate and sodium butyrate. United States: N. p., 2014. Web. doi:10.1016/J.YEXCR.2014.01.024.
Saldanha, Sabita N., E-mail: sabivan@uab.edu, Department of Biological Sciences, Alabama State University, Montgomery, AL 36104, Kala, Rishabh, Tollefsbol, Trygve O., E-mail: trygve@uab.edu, Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35294, Comprehensive Center for Healthy Aging, University of Alabama at Birmingham, Birmingham, AL 35294, Nutrition Obesity Research Center, University of Alabama at Birmingham, Birmingham, AL 35294, & Comprehensive Diabetes Research Center, University of Alabama at Birmingham, Birmingham, AL 35294. Molecular mechanisms for inhibition of colon cancer cells by combined epigenetic-modulating epigallocatechin gallate and sodium butyrate. United States. https://doi.org/10.1016/J.YEXCR.2014.01.024
Saldanha, Sabita N., E-mail: sabivan@uab.edu, Department of Biological Sciences, Alabama State University, Montgomery, AL 36104, Kala, Rishabh, Tollefsbol, Trygve O., E-mail: trygve@uab.edu, Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35294, Comprehensive Center for Healthy Aging, University of Alabama at Birmingham, Birmingham, AL 35294, Nutrition Obesity Research Center, University of Alabama at Birmingham, Birmingham, AL 35294, and Comprehensive Diabetes Research Center, University of Alabama at Birmingham, Birmingham, AL 35294. 2014. "Molecular mechanisms for inhibition of colon cancer cells by combined epigenetic-modulating epigallocatechin gallate and sodium butyrate". United States. https://doi.org/10.1016/J.YEXCR.2014.01.024.
@article{osti_22395897,
title = {Molecular mechanisms for inhibition of colon cancer cells by combined epigenetic-modulating epigallocatechin gallate and sodium butyrate},
author = {Saldanha, Sabita N., E-mail: sabivan@uab.edu and Department of Biological Sciences, Alabama State University, Montgomery, AL 36104 and Kala, Rishabh and Tollefsbol, Trygve O., E-mail: trygve@uab.edu and Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35294 and Comprehensive Center for Healthy Aging, University of Alabama at Birmingham, Birmingham, AL 35294 and Nutrition Obesity Research Center, University of Alabama at Birmingham, Birmingham, AL 35294 and Comprehensive Diabetes Research Center, University of Alabama at Birmingham, Birmingham, AL 35294},
abstractNote = {Bioactive compounds are considered safe and have been shown to alter genetic and epigenetic profiles of tumor cells. However, many of these changes have been reported at molecular concentrations higher than physiologically achievable levels. We investigated the role of the combinatorial effects of epigallocatechin gallate (EGCG), a predominant polyphenol in green tea, and sodium butyrate (NaB), a dietary microbial fermentation product of fiber, in the regulation of survivin, which is an overexpressed anti-apoptotic protein in colon cancer cells. For the first time, our study showed that the combination treatment induced apoptosis and cell cycle arrest in RKO, HCT-116 and HT-29 colorectal cancer cells. This was found to be regulated by the decrease in HDAC1, DNMT1, survivin and HDAC activity in all three cell lines. A G2/M arrest was observed for RKO and HCT-116 cells, and G1 arrest for HT-29 colorectal cancer cells for combinatorial treatment. Further experimentation of the molecular mechanisms in RKO colorectal cancer (CRC) cells revealed a p53-dependent induction of p21 and an increase in nuclear factor kappa B (NF-κB)-p65. An increase in double strand breaks as determined by gamma-H2A histone family member X (γ-H2AX) protein levels and induction of histone H3 hyperacetylation was also observed with the combination treatment. Further, we observed a decrease in global CpG methylation. Taken together, these findings suggest that at low and physiologically achievable concentrations, combinatorial EGCG and NaB are effective in promoting apoptosis, inducing cell cycle arrest and DNA-damage in CRC cells. - Highlights: • EGCG and NaB as a combination inhibits colorectal cancer cell proliferation. • The combination treatment induces DNA damage, G2/M and G1 arrest and apoptosis. • Survivin is effectively down-regulated by the combination treatment. • p21 and p53 expressions are induced by the combination treatment. • Epigenetic proteins DNMT1 and HDAC1 are effectively down-regulated by the treatment.},
doi = {10.1016/J.YEXCR.2014.01.024},
url = {https://www.osti.gov/biblio/22395897}, journal = {Experimental Cell Research},
issn = {0014-4827},
number = 1,
volume = 324,
place = {United States},
year = {Thu May 15 00:00:00 EDT 2014},
month = {Thu May 15 00:00:00 EDT 2014}
}