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 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.
authors.affiliation: Chest Clinic, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Tzu-Chin
authors.initials: TC
authors.lastname: Wu
authors.affiliation: Department of Nutritional Science, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Yi-Chin
authors.initials: YC
authors.lastname: Lin
authors.affiliation: Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan.
authors.forename: Hsiao-Ling
authors.initials: HL
authors.lastname: Chen
authors.affiliation: Department of Nutritional Science, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Pei-Ru
authors.initials: PR
authors.lastname: Huang
authors.affiliation: Department of Nutritional Science, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Shang-Yu
authors.initials: SY
authors.lastname: Liu
authors.affiliation: Department of Nutritional Science, Chung Shan Medical University, Taichung, Taiwan; Department of Nutrition, Chung Shan Medical University Hospital, Taichung, Taiwan. Electronic address: suzyyeh@csmu.edu.tw.
authors.forename: Shu-Lan
authors.initials: SL
authors.lastname: Yeh
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D016158:Genes, p53 / Q000187:drug effects* / Q000502:physiology; D019833:Genistein / Q000008:administration & dosage*; D051548:Histone Acetyltransferases / Q000096:biosynthesis*; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000201:enzymology*; D051379:Mice; D008819:Mice, Nude; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D006877:Hydroxamic Acids; C012589:trichostatin A; D019833:Genistein; D051548:Histone Acetyltransferases
keywords: Genistein; Histone acetyltransferase; Human lung cancer cells; Trichostatin A