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创伤酸对人乳腺癌 MCF-7 细胞的毒性作用机制。

Traumatic acid toxicity mechanisms in human breast cancer MCF-7 cells.

机构信息

Division of Chemistry, Biology and Biotechnology, Białystok University of Technology, Białystok, 15-351, Poland.

Department of Pharmaceutical Biochemistry, Medical University of Białystok, Białystok, 15-222, Poland.

出版信息

Regul Toxicol Pharmacol. 2019 Aug;106:137-146. doi: 10.1016/j.yrtph.2019.04.023. Epub 2019 May 2.

Abstract

Traumatic acid (TA) - an oxidative derivative of unsaturated fatty acids, belongs to the cytokinins category - a group of plant hormones, which play an important role in growth and development. Previously we demonstrated its positive influence on oxidative stress parameters in normal human fibroblasts, therefore we decided to investigate its activity in cancer cells. MCF-7 breast cancer cell line was chosen as an experimental model because of proved association between the consumption of dietary fat and the incidence of breast cancer. TA cytotoxicity and its effects on MCF-7 cells proliferation, viability, apoptosis/necrosis, thiol group content, lipid peroxidation, reduced/oxidized glutathione (GSH/GSSG) and ROS (reactive oxygen species) content was examined. The results show a significant effect of TA on tested parameters. TA caused a decrease in cells proliferation and viability, GSH/GSSG ratio and thiol group content. It increases caspase 7 activity, membrane lipid peroxidation and ROS content, simultaneously reducing breast cancer cell growth through oxidative stress influence on apoptosis. The present findings reveal that TA exhibits multiple and complex activity in MCF-7 breast cancer cells and it exhibits potential anticancer properties and tumor preventive activity.

摘要

创伤酸(TA) - 不饱和脂肪酸的氧化衍生物,属于细胞分裂素类 - 一组植物激素,在生长和发育中起重要作用。我们之前证明了它对正常人成纤维细胞氧化应激参数的积极影响,因此我们决定研究它在癌细胞中的活性。MCF-7 乳腺癌细胞系被选为实验模型,因为已经证明饮食脂肪的消耗与乳腺癌的发病率之间存在关联。TA 的细胞毒性及其对 MCF-7 细胞增殖、活力、细胞凋亡/坏死、巯基含量、脂质过氧化、还原/氧化型谷胱甘肽(GSH/GSSG)和 ROS(活性氧)含量的影响进行了研究。结果表明 TA 对测试参数有显著影响。TA 导致细胞增殖和活力、GSH/GSSG 比值和巯基含量降低。它增加了半胱天冬酶 7 的活性、膜脂质过氧化和 ROS 含量,同时通过氧化应激对细胞凋亡的影响抑制乳腺癌细胞的生长。本研究结果表明 TA 在 MCF-7 乳腺癌细胞中表现出多种复杂的活性,具有潜在的抗癌特性和肿瘤预防活性。

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