Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells.

Autor: Dos Santos PWDS; Department of Clinical Analysis, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Av. do Café - Vila Monte Alegre, Ribeirão Preto, SP, 14040-903, Brazil. Electronic address: patrickwsantos@gmail.com., Machado ART; Department of Clinical Analysis, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Av. do Café - Vila Monte Alegre, Ribeirão Preto, SP, 14040-903, Brazil. Electronic address: anaritatmachado@usp.br., De Grandis RA; Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes, 3900 - Vila Monte Alegre, Ribeirão Preto, SP, 14049-900, Brazil. Electronic address: degrandis.rone@gmail.com., Ribeiro DL; Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes, 3900 - Vila Monte Alegre, Ribeirão Preto, SP, 14049-900, Brazil. Electronic address: diegoluisribeiro@usp.br., Tuttis K; Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes, 3900 - Vila Monte Alegre, Ribeirão Preto, SP, 14049-900, Brazil. Electronic address: kattuttis@gmail.com., Morselli M; Department of Molecular, Cell, and Developmental Biology, University of California at Los Angeles, 610 Charles E Young Dr S, Los Angeles, CA, 90095, USA. Electronic address: mmorselli@g.ucla.edu., Aissa AF; Department of Clinical Analysis, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Av. do Café - Vila Monte Alegre, Ribeirão Preto, SP, 14040-903, Brazil. Electronic address: afaissa@gmail.com., Pellegrini M; Department of Molecular, Cell, and Developmental Biology, University of California at Los Angeles, 610 Charles E Young Dr S, Los Angeles, CA, 90095, USA. Electronic address: matteop@mcdb.ucla.edu., Antunes LMG; Department of Clinical Analysis, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Av. do Café - Vila Monte Alegre, Ribeirão Preto, SP, 14040-903, Brazil. Electronic address: lusania@fcfrp.usp.br.
Jazyk: angličtina
Zdroj: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association [Food Chem Toxicol] 2020 Feb; Vol. 136, pp. 111047. Date of Electronic Publication: 2019 Dec 12.
DOI: 10.1016/j.fct.2019.111047
Abstrakt: Abnormal epigenetic alterations are one of the keystones of cancer development. Epigenetic targeting drugs have become a promising and effective cancer therapy strategy. However, due to the high toxicity and unclear mechanisms of action of these drugs, natural compounds that cause epigenetic modulation have also been studied. Sulforaphane (SFN) is a promising bioactive compound for epigenetic targeting therapy. In this study, we investigate the effects of SFN on gene expression and DNA methylation in human hepatocellular carcinoma cells (HepG2). Using high throughput technologies in combination with cell-based assays, we find SFN is a potent anticancer agent, as it induces DNA damage, mitotic spindle abnormalities followed by apoptosis and proliferation inhibition in HepG2 cells. Our results show the upregulation of DNA damage response and cell cycle checkpoint genes. Also, we find the downregulation of cellular pathways frequently overexpressed in human cancer. As expected, SFN exerts epigenetic modulation effects by inhibiting histone deacetylases (HDACs). SFN might affect the activity of oncogenic transcription factors through methylation of its binding sites motifs. Our findings offer insights into SFN chemopreventive molecular effects in HepG2 cells and highlight SFN as a valuable natural approach to cancer therapy for future investigation.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2019 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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