没食子酸丙酯通过诱导芬顿反应增强对 HepG2 细胞系的细胞毒性作用：一项体外和计算研究。

The Cytotoxic Effect of Thymoquinone Enhance on HepG2 Cell Line due to Induction of Fenton Reaction by Hydrogen Peroxide: An In Vitro and In Silico Study.

机构信息

Medicinal Plants and Natural Products Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.

Department of Pharmacology and Toxicology, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran.

出版信息

Asian Pac J Cancer Prev. 2023 May 1;24(5):1809-1815. doi: 10.31557/APJCP.2023.24.5.1809.

DOI:10.31557/APJCP.2023.24.5.1809

PMID:37247304

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10495912/

Abstract

OBJECTIVE

Thymoquinone (TQ) is a component derived from the volatile oil of Nigella sativa. Fenton reaction induction is a well-known strategy to prevent the growth of cancer cells which can stimulate by hydrogen peroxide. This study was designed to investigate the TQ effects on hydrogen peroxide-induced cytotoxicity.

METHODS

In this study, HepG2 cell survival, reactive oxygen species (ROS) production, cell membrane integrity, and changes of superoxide dismutase (SOD)/ catalase (CAT) activity were evaluated following incubation of HepG2 cells with 31 μM hydrogen peroxide and different concentrations of TQ (18.5, 37 and 75 μM). In addition, molecular docking studies on the interference of TQ with CAT/SOD enzymes were investigated.

RESULTS

Our findings showed that TQ low concentration can increase the survival of HepG2 cells when exposed to hydrogen peroxide, and on the contrary, its high concentration can potentiate cytotoxicity induced by hydrogen peroxide. The TQ alongside hydrogen peroxide increased the production of ROS, which was related to increase CAT and SOD activity in the HepG2 cells. Molecular docking findings showed that TQ effects on the formation of free radicals were not related to its chemical interference with the structure of the SOD/CAT molecules.

CONCLUSION

Fenton reaction induction may increase the effectiveness of TQ in preventing HepG2 cells proliferation.

摘要

目的

百里香醌（TQ）是从黑种草挥发油中提取的一种成分。芬顿反应诱导是一种众所周知的策略，可以防止由过氧化氢刺激的癌细胞生长。本研究旨在探讨 TQ 对过氧化氢诱导的细胞毒性的影响。

方法

在这项研究中，孵育 HepG2 细胞用 31 μM 过氧化氢和不同浓度的 TQ（18.5、37 和 75 μM）后，评估 HepG2 细胞的存活率、活性氧（ROS）产生、细胞膜完整性以及超氧化物歧化酶（SOD）/过氧化氢酶（CAT）活性的变化。此外，还研究了 TQ 对 CAT/SOD 酶干扰的分子对接研究。

结果

我们的研究结果表明，TQ 低浓度可增加暴露于过氧化氢的 HepG2 细胞的存活率，而高浓度则可增强过氧化氢诱导的细胞毒性。TQ 与过氧化氢一起增加了 ROS 的产生，这与 HepG2 细胞中 CAT 和 SOD 活性的增加有关。分子对接研究结果表明，TQ 对自由基形成的影响与其对 SOD/CAT 分子结构的化学干扰无关。