Up and down-regulation of mRNA in the cytotoxicity and genotoxicity of Plumbagin in HepG2/C3A.
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.
['Vaz Crippa|Giovanna|G|', 'Zanetti|Thalita Alves|TA|', 'Biazi|Bruna Isabela|BI|', 'Baranoski|Adrivânio|A|', 'Marques|Lilian Areal|LA|', 'Coatti|Giuliana Castello|GC|', 'Lepri|Sandra Regina|SR|', 'Mantovani|Mário Sérgio|MS|']
D000969:Antinematodal Agents D002470:Cell Survival D020552:Comet Assay D004249:DNA Damage D015536:Down-Regulation D056945:Hep G2 Cells D006801:Humans D009285:Naphthoquinones D012333:RNA, Messenger
Genotoxicity Biomarker Autophagy Gene expression