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Title: The enhancing effect of genistein on apoptosis induced by trichostatin A in lung cancer cells with wild type p53 genes is associated with upregulation of histone acetyltransferase

Abstract

Genistein has been shown to enhance the antitumor activity of trichostatin A (TSA) in human lung carcinoma A549 cells. However, whether the combined treatment exerts the same effect in other lung cancer cells is unclear. In the present study we first compared the enhancing effect of genistein on the antitumor effect of TSA in ABC-1, NCI-H460 (H460) and A549 cells. Second, we investigated whether the effects of genistein are associated with increased histone/non-histone protein acetylation. We found that the enhancing effect of genistein on cell-growth-arrest in ABC-1 cells (p53 mutant) was less than in A549 and H460 cells. Genistein enhanced TSA induced apoptosis in A549 and H460 cells rather than in ABC-1 cells. After silencing p53 expression in A549 and H460 cells, the enhancing effect of genistein was diminished. In addition, genistein increased TSA-induced histone H3/H4 acetylation in A549 and H460 cells. Genistein also increased p53 acetylation in H460 cells. The inhibitor of acetyltransferase, anacardic acid, diminished the enhancing effect of genistein on all TSA-induced histone/p53 acetylation and apoptosis. Genistein in combination with TSA increased the expression of p300 protein, an acetyltransferase, in A549 and NCI-H460 cells. Furthermore, we demonstrated that genistein also enhanced the antitumor effect of genistein inmore » A549-tumor-bearing mice. Taken together, these results suggest that the enhancing effects of genistein on TSA-induced apoptosis in lung cancer cells were p53-dependent and were associated with histone/non-histone protein acetylation. - Highlights: • Genistein enhances the antitumor effect of TSA through p53-associated pathways. • Genistein enhances TSA-induced histone acetylation commonly. • An acetyltransferase inhibitor diminishes the antitumor effect of genistein + TSA. • TSA in combination with genistein increases the expression of p300. • Genistein given by i.p. injection increases the antitumor effect of TSA in vivo.« less

Authors:
 [1];  [2];  [3]; ;  [2];  [2];  [4]
  1. Chest Clinic, Chung Shan Medical University Hospital, Taichung, Taiwan (China)
  2. Department of Nutritional Science, Chung Shan Medical University, Taichung, Taiwan (China)
  3. Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan (China)
  4. (China)
Publication Date:
OSTI Identifier:
22687893
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 292; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ACETYLATION; APOPTOSIS; CARCINOMAS; GENES; HISTONES; IN VIVO; INJECTION; LUNGS; MICE

Citation Formats

Wu, Tzu-Chin, Lin, Yi-Chin, Chen, Hsiao-Ling, Huang, Pei-Ru, Liu, Shang-Yu, Yeh, Shu-Lan, E-mail: suzyyeh@csmu.edu.tw, and Department of Nutrition, Chung Shan Medical University Hospital, Taichung, Taiwan. The enhancing effect of genistein on apoptosis induced by trichostatin A in lung cancer cells with wild type p53 genes is associated with upregulation of histone acetyltransferase. United States: N. p., 2016. Web. doi:10.1016/J.TAAP.2015.12.028.
Wu, Tzu-Chin, Lin, Yi-Chin, Chen, Hsiao-Ling, Huang, Pei-Ru, Liu, Shang-Yu, Yeh, Shu-Lan, E-mail: suzyyeh@csmu.edu.tw, & Department of Nutrition, Chung Shan Medical University Hospital, Taichung, Taiwan. The enhancing effect of genistein on apoptosis induced by trichostatin A in lung cancer cells with wild type p53 genes is associated with upregulation of histone acetyltransferase. United States. doi:10.1016/J.TAAP.2015.12.028.
Wu, Tzu-Chin, Lin, Yi-Chin, Chen, Hsiao-Ling, Huang, Pei-Ru, Liu, Shang-Yu, Yeh, Shu-Lan, E-mail: suzyyeh@csmu.edu.tw, and Department of Nutrition, Chung Shan Medical University Hospital, Taichung, Taiwan. Mon . "The enhancing effect of genistein on apoptosis induced by trichostatin A in lung cancer cells with wild type p53 genes is associated with upregulation of histone acetyltransferase". United States. doi:10.1016/J.TAAP.2015.12.028.
@article{osti_22687893,
title = {The enhancing effect of genistein on apoptosis induced by trichostatin A in lung cancer cells with wild type p53 genes is associated with upregulation of histone acetyltransferase},
author = {Wu, Tzu-Chin and Lin, Yi-Chin and Chen, Hsiao-Ling and Huang, Pei-Ru and Liu, Shang-Yu and Yeh, Shu-Lan, E-mail: suzyyeh@csmu.edu.tw and Department of Nutrition, Chung Shan Medical University Hospital, Taichung, Taiwan},
abstractNote = {Genistein has been shown to enhance the antitumor activity of trichostatin A (TSA) in human lung carcinoma A549 cells. However, whether the combined treatment exerts the same effect in other lung cancer cells is unclear. In the present study we first compared the enhancing effect of genistein on the antitumor effect of TSA in ABC-1, NCI-H460 (H460) and A549 cells. Second, we investigated whether the effects of genistein are associated with increased histone/non-histone protein acetylation. We found that the enhancing effect of genistein on cell-growth-arrest in ABC-1 cells (p53 mutant) was less than in A549 and H460 cells. Genistein enhanced TSA induced apoptosis in A549 and H460 cells rather than in ABC-1 cells. After silencing p53 expression in A549 and H460 cells, the enhancing effect of genistein was diminished. In addition, genistein increased TSA-induced histone H3/H4 acetylation in A549 and H460 cells. Genistein also increased p53 acetylation in H460 cells. The inhibitor of acetyltransferase, anacardic acid, diminished the enhancing effect of genistein on all TSA-induced histone/p53 acetylation and apoptosis. Genistein in combination with TSA increased the expression of p300 protein, an acetyltransferase, in A549 and NCI-H460 cells. Furthermore, we demonstrated that genistein also enhanced the antitumor effect of genistein in A549-tumor-bearing mice. Taken together, these results suggest that the enhancing effects of genistein on TSA-induced apoptosis in lung cancer cells were p53-dependent and were associated with histone/non-histone protein acetylation. - Highlights: • Genistein enhances the antitumor effect of TSA through p53-associated pathways. • Genistein enhances TSA-induced histone acetylation commonly. • An acetyltransferase inhibitor diminishes the antitumor effect of genistein + TSA. • TSA in combination with genistein increases the expression of p300. • Genistein given by i.p. injection increases the antitumor effect of TSA in vivo.},
doi = {10.1016/J.TAAP.2015.12.028},
journal = {Toxicology and Applied Pharmacology},
number = ,
volume = 292,
place = {United States},
year = {Mon Feb 01 00:00:00 EST 2016},
month = {Mon Feb 01 00:00:00 EST 2016}
}