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

Publication date: Available online 10 January 2020Source: Environmental Toxicology and PharmacologyAuthor(s): Giovanna Vaz Crippa, Thalita Alves Zanetti, Bruna Isabela Biazi, Adrivânio Baranoski, Lilian Areal Marques, Giuliana Castello Coatti, Sandra Regina Lepri, Mário Sérgio MantovaniAbstractStudies 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, there...
Source: Environmental Toxicology and Pharmacology - Category: Environmental Health Source Type: research