Up and down-regulation of mRNA in the cytotoxicity and genotoxicity of Plumbagin in HepG2/C3A.

Autor: Vaz Crippa G; Department of General Biology, Center of Biological Sciences, Londrina State University - UEL, Rodovia Celso Garcia Cid, Pr 445 Km 380, Londrina, Paraná, Brazil., Zanetti TA; Department of General Biology, Center of Biological Sciences, Londrina State University - UEL, Rodovia Celso Garcia Cid, Pr 445 Km 380, Londrina, Paraná, Brazil., Biazi BI; Department of General Biology, Center of Biological Sciences, Londrina State University - UEL, Rodovia Celso Garcia Cid, Pr 445 Km 380, Londrina, Paraná, Brazil., Baranoski A; Department of General Biology, Center of Biological Sciences, Londrina State University - UEL, Rodovia Celso Garcia Cid, Pr 445 Km 380, Londrina, Paraná, Brazil., Marques LA; Department of General Biology, Center of Biological Sciences, Londrina State University - UEL, Rodovia Celso Garcia Cid, Pr 445 Km 380, Londrina, Paraná, Brazil., Coatti GC; Human Genome and Stem-Cell Research Center, Institute of Biosciences, University of São Paulo - USP, Rua do Matão - Travessa 13, n. 106, São Paulo, São Paulo, Brazil., Lepri SR; Department of General Biology, Center of Biological Sciences, Londrina State University - UEL, Rodovia Celso Garcia Cid, Pr 445 Km 380, Londrina, Paraná, Brazil., Mantovani MS; Department of General Biology, Center of Biological Sciences, Londrina State University - UEL, Rodovia Celso Garcia Cid, Pr 445 Km 380, Londrina, Paraná, Brazil. Electronic address: mantovani@pq.cnpq.br.
Jazyk: angličtina
Zdroj: Environmental toxicology and pharmacology [Environ Toxicol Pharmacol] 2020 Apr; Vol. 75, pp. 103328. Date of Electronic Publication: 2020 Jan 10.
DOI: 10.1016/j.etap.2020.103328
Abstrakt: Studies that evaluated the mechanisms of action of Plumbagin (PLB) and its toxicity may contribute to future therapeutic applications of this compound. We investigate biomarker important in the mechanisms of action correlate the expression of mRNA with the cytotoxic and genotoxic effects of PLB on HepG2/C3A. In the analysis of cytotoxicity, PLB decreased cell viability and membrane integrity at concentrations ≥ 15μM. Xenobiotic-metabolizing system showed strong mRNA induction of CYP1A1, CYP1A2, and CYP3A4, suggesting extensive metabolization. PLB induced apoptosis and an increase in the mRNA expression of genes BBC3, CASP3, and CASP8. At a concentration of 15μM, there was a reduction in the expression of PARP1 mRNA and an increase in the expression of BECN1 mRNA, suggesting that PLB may also induce cell death by autophagy. PLB induced an arrest at the G2/M phase due to DNA damage, as observed in the comet assay. This damage is associated with the increased mRNA expression of genes p21, GADD45A, and H2AFX and with changes in the expression of proteins H2AX, p21, p53, Chk1, and Chk2. These results allow a better understanding of the cellular action of PLB and of its toxicity, thereby contributing to the development of PLB-based drugs, with markers of mRNA expression possibly playing a role as indicators for monitoring toxicity in human cells.
Competing Interests: Declaration of Competing Interest None declared.
(Copyright © 2020 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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