Trepiana Jenifer, Ruiz-Larrea M Begoña, Ruiz-Sanz José Ignacio
Department of Physiology, Medicine and Nursing School, University of the Basque Country UPV/EHU, Leioa 48940, Spain.
Heliyon. 2018 Jun 29;4(6):e00675. doi: 10.1016/j.heliyon.2018.e00675. eCollection 2018 Jun.
Currently natural products derived from plants are receiving huge attention because of their antitumor activities. In previous work we reported that an aqueous leaf extract of induced toxicity in HepG2. The present study focuses on the mechanisms of the cytotoxic actions induced by the extract. Results showed that was innocuous in non-transformed human HH4 hepatocytes. In HepG2 it caused deregulation of antioxidant status (increasing superoxide dismutase expression and decreasing glutathione levels and glutathione peroxidase activity) and accumulation of reactive oxygen species, particularly hydrogen peroxide. The extract induced a) cell cycle arrest at G/M phase, b) phosphorylation of ATM (protein kinase ataxia-telangiectasia mutated) and γH2AX (γ-histone family 2A variant), c) caspase-3 activation, and e) deregulation of the Bax/Bcl family, increasing pro-apoptotic proteins. ATM did not seem to be involved in γH2AX activation. Co-incubation with catalase prevented the alterations elicited by in HepG2. Taking together, these results indicate that hydrogen peroxide mediates the HepG2 cytotoxic response and provide evidence for more in-depth studies of the signaling involved.
目前，源自植物的天然产物因其抗肿瘤活性而备受关注。在之前的工作中，我们报道了[植物名称]的叶水提取物对HepG2细胞具有毒性。本研究聚焦于该提取物诱导细胞毒性作用的机制。结果表明，[提取物名称]对未转化的人HH4肝细胞无毒害作用。在HepG2细胞中，它导致抗氧化状态失调（超氧化物歧化酶表达增加，谷胱甘肽水平和谷胱甘肽过氧化物酶活性降低）以及活性氧物质的积累，尤其是过氧化氢。该提取物诱导了：a）细胞周期在G/M期停滞；b）共济失调毛细血管扩张症突变蛋白激酶（ATM）和γH2AX（γ组蛋白家族2A变体）的磷酸化；c）半胱天冬酶-3的激活；以及e）Bax/Bcl家族失调，促凋亡蛋白增加。ATM似乎未参与γH2AX的激活。与过氧化氢酶共同孵育可防止[提取物名称]在HepG2细胞中引发的改变。综上所述，这些结果表明过氧化氢介导了HepG2细胞的细胞毒性反应，并为深入研究相关信号传导提供了证据。
