M. A. Savitskaya, I. I. Zakharov, A. A. Saidova, E. A. Smirnova, G. E. Onishchenko
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引用次数: 0
Abstract
Vitamin E succinate (VES) is a potential antitumor agent known for its targeted effect on the mitochondria of tumor cells. However, data on the proapoptotic mechanism of action of VES are ambiguous, and the effect of VES on normal nontumorigenic cells has not been fully studied. Previously, it was possible to demonstrate the induction of apoptosis by the mitochondrial mechanism under the action of VES on human epidermoid carcinoma A431 cells. The purpose of this work is to investigate the effect of VES on nontumorigenic cells and to identify common mechanisms that are characteristic of both normal and tumor cells, as well as mechanisms that manifest themselves only in one of the categories of cells. To achieve this goal, the effect of VES on such organelles as endoplasmic reticulum (ER) and the Golgi apparatus and the expression of genes associated with ER stress were analyzed, and also the reactive oxygen species (ROS) content and accumulation of lipid droplets in the cytoplasm in human epidermoid carcinoma A431 cells and HaCaT immortalized human keratinocytes were assessed. It was shown that, in cells of both lines, there are signs of ER stress, the content of ROS and lipid inclusions and the number of apoptotic cells increase. At the same time, the key difference between the mechanisms of induction of apoptotic death of A431 and HaCaT cells under the influence of VES lies in the reaction of mitochondria: in A431 cells, apoptotic death is triggered by the mitochondrial mechanism, while HaCaT cells enter apoptosis without the participation of mitochondria. Thus, the targets of VES on normal and tumor cells may differ and, possibly, can complement each other in inducing apoptosis.
摘要维生素 E 琥珀酸酯（VES）是一种潜在的抗肿瘤药物，因其对肿瘤细胞线粒体的靶向作用而闻名。然而，有关 VES 促凋亡作用机制的数据并不明确，而且 VES 对正常非致癌细胞的影响尚未得到充分研究。此前，在 VES 对人类表皮样癌 A431 细胞的作用下，线粒体机制诱导了细胞凋亡。这项工作的目的是研究 VES 对非致瘤细胞的影响，并找出正常细胞和肿瘤细胞所特有的共同机制，以及仅在其中一类细胞中表现出来的机制。为实现这一目标，研究人员分析了 VES 对内质网（ER）和高尔基体等细胞器的影响以及与 ER 应激相关的基因的表达，还评估了人表皮样癌 A431 细胞和 HaCaT 永生人角质形成细胞中活性氧（ROS）的含量和细胞质中脂滴的积累。结果表明，两种细胞系的细胞都出现了 ER 应激迹象，ROS 和脂质包涵体的含量以及凋亡细胞的数量都有所增加。同时，在 VES 的影响下，A431 和 HaCaT 细胞凋亡诱导机制的关键区别在于线粒体的反应：在 A431 细胞中，凋亡是由线粒体机制触发的，而 HaCaT 细胞进入凋亡则没有线粒体的参与。因此，VES 对正常细胞和肿瘤细胞的作用靶点可能不同，也可能在诱导细胞凋亡方面相互补充。
期刊介绍：
The journal publishes papers on vast aspects of cell research, including morphology, biochemistry, biophysics, genetics, molecular biology, immunology. The journal accepts original experimental studies, theoretical articles suggesting novel principles and approaches, presentations of new hypotheses, reviews highlighting major developments in cell biology, discussions. The main objective of the journal is to provide a competent representation and integration of research made on cells (animal and plant cells, both in vivo and in cell culture) offering insight into the structure and functions of live cells as a whole. Characteristically, the journal publishes articles on biology of free-living and parasitic protists, which, unlike Metazoa, are eukaryotic organisms at the cellular level of organization.
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