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.

评估Plumbagin（PLB）作用机理及其毒性的研究可能有助于该化合物的未来治疗应用。我们调查在作用机制中重要的生物标志物将mRNA的表达与PLB对HepG2 / C3A的细胞毒性和遗传毒性作用相关。在细胞毒性分析中，浓度≥15μM时，PLB会降低细胞活力和膜完整性。异种生物代谢系统显示出对CYP1A1，CYP1A2和CYP3A4的强烈mRNA诱导，表明其广泛代谢。PLB诱导细胞凋亡并增加基因BBC3，CASP3和CASP8的mRNA表达。在浓度为15μM时，PARP1 mRNA的表达减少，而BECN1 mRNA的表达增加，这表明PLB也可能通过自噬诱导细胞死亡。正如彗星试验中所观察到的，PLB由于DNA损伤而在G2 / M期引起停滞。这种损害与基因p21，GADD45A和H2AFX的mRNA表达增加有关以及蛋白质H2AX，p21，p53，Chk1和Chk2表达的变化。这些结果使人们能够更好地了解PLB的细胞作用及其毒性，从而有助于开发基于PLB的药物，mRNA表达的标志物可能起着监测人类细胞毒性的指示剂的作用。