Abstract

In the present study, cytotoxic (apoptotic and necrotic), antioxidant, prooxidant, genotoxic, and apoptosis-related genes expression modulatory effects of physodic acid (PA) isolated from Pseudevernia furfuracea on cancerous (HepG2) and healthy (THLE2) human liver cells were evaluated. Cytotoxic effects PA obtained from P. furfuracea on HepG2 and THLE2 cells were tested via MTT and LDH analyses. In order to determine genotoxic effect of PA, 8-OH-dG levels in the cells were measured. In addition, apoptotic or necrotic effects of PA on the hepatic cells were determined by qRT-PCR analysis. Cytotoxicity analyses revealed the cytotoxic effect of PA on HepG2 cells, which is much higher than THLE2 cells. Gene expression studies demonstrated the apoptotic effects of PA on HepG2 cells through both extrinsic and intrinsic pathways. PA increased the antioxidant capacity of THLE2 cells with increasing concentrations, which describes its antioxidant power. Additionally, none of the tested levels of PA caused oxidative DNA damage on THLE2 cells, but its high concentration increased genetic damages on HepG2. Taken together, P. furfuracea lichen and its metabolite, PA, would be a promising alternative for complementary treatments against liver cancer.

摘要

在本研究中，细胞毒性（凋亡和坏死）、抗氧化、促氧化、基因毒性和凋亡相关基因表达的调节作用是从Pseudevernia furfuracea中分离出的植酸 (PA)对癌性 (HepG2) 和健康 (THLE2) 人肝细胞的影响。评估。来自P. furfuracea的细胞毒性作用 PA通过 MTT 和 LDH 分析对 HepG2 和 THLE2 细胞进行了测试。为了确定 PA 的遗传毒性作用，测量了细胞中的 8-OH-dG 水平。此外，通过 qRT-PCR 分析确定 PA 对肝细胞的凋亡或坏死作用。细胞毒性分析显示 PA 对 HepG2 细胞的细胞毒性作用远高于 THLE2 细胞。基因表达研究通过外在和内在途径证明了 PA 对 HepG2 细胞的凋亡作用。PA 随着浓度的增加增加了 THLE2 细胞的抗氧化能力，这描述了它的抗氧化能力。此外，所测试的 PA 水平均未对 THLE2 细胞造成氧化性 DNA 损伤，但其高浓度会增加对 HepG2 的遗传损伤。综合起来，P. furfuracea地衣及其代谢物 PA 将成为肝癌补充治疗的有希望的替代品。