药物抗坏血酸、氯喹和白藜芦醇的交错抗癌作用。

IF 5 3区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
BioFactors Pub Date : 2024-03-15 DOI:10.1002/biof.2050
Kinga Makk-Merczel, Dóra Varga, Péter Hajdinák, András Szarka
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引用次数: 0

摘要

目前,一旦确诊为 KRAS 突变型胰腺导管腺癌(PDAC)就意味着死亡,因此寻找有效的治疗方案是一个紧迫的问题。在这里,我们介绍了抗坏血酸、氯喹和白藜芦醇联合治疗对 PDAC 细胞株产生的协同细胞毒性作用。所观察到的协同细胞毒性是所有被研究癌细胞株的普遍特征,与 KRAS 突变状态无关,似乎也与氯喹的自噬抑制作用无关。此外,细胞凋亡和坏死似乎也不可能在氯喹的细胞毒性中发挥任何作用。药物抗坏血酸和白藜芦醇都会导致双链 DNA 断裂,并伴随细胞周期的停滞。白藜芦醇诱导的细胞毒性似乎与活性氧(ROS)的生成无关,并伴有 Caspase-3/7 活性的显著升高,而药物抗坏血酸诱导的细胞毒性则表现出强烈的 ROS 依赖性,但证明与 Caspase 无关。我们的研究结果尤为重要,因为抗坏血酸和白藜芦醇都是天然化合物,对正常细胞没有明显的有害影响,而氯喹是一种已知的抗疟药物,很容易被重新利用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

The interlacing anticancer effect of pharmacologic ascorbate, chloroquine, and resveratrol

The interlacing anticancer effect of pharmacologic ascorbate, chloroquine, and resveratrol

The interlacing anticancer effect of pharmacologic ascorbate, chloroquine, and resveratrol

Currently, a diagnosis with KRAS mutant pancreatic ductal adenocarcinoma (PDAC) means a death warrant, so finding efficient therapeutic options is a pressing issue. Here, we presented that pharmacologic ascorbate, chloroquine and resveratrol co-treatment exerted a synergistic cytotoxic effect on PDAC cell lines. The observed synergistic cytotoxicity was a general feature in all investigated cancer cell lines independent of the KRAS mutational status and seems to be independent of the autophagy inhibitory effect of chloroquine. Furthermore, it seems that apoptosis and necroptosis are also not likely to play any role in the cytotoxicity of chloroquine. Both pharmacologic ascorbate and resveratrol caused double-strand DNA breaks accompanied by cell cycle arrest. It seems resveratrol-induced cytotoxicity is independent of reactive oxygen species (ROS) generation and accompanied by a significant elevation of caspase-3/7 activity, while pharmacologic ascorbate-induced cytotoxicity shows strong ROS dependence but proved to be caspase-independent. Our results are particularly important since ascorbate and resveratrol are natural compounds without significant harmful effects on normal cells, and chloroquine is a known antimalarial drug that can easily be repurposed.

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来源期刊
BioFactors
BioFactors 生物-内分泌学与代谢
CiteScore
11.50
自引率
3.30%
发文量
96
审稿时长
6-12 weeks
期刊介绍: BioFactors, a journal of the International Union of Biochemistry and Molecular Biology, is devoted to the rapid publication of highly significant original research articles and reviews in experimental biology in health and disease. The word “biofactors” refers to the many compounds that regulate biological functions. Biological factors comprise many molecules produced or modified by living organisms, and present in many essential systems like the blood, the nervous or immunological systems. A non-exhaustive list of biological factors includes neurotransmitters, cytokines, chemokines, hormones, coagulation factors, transcription factors, signaling molecules, receptor ligands and many more. In the group of biofactors we can accommodate several classical molecules not synthetized in the body such as vitamins, micronutrients or essential trace elements. In keeping with this unified view of biochemistry, BioFactors publishes research dealing with the identification of new substances and the elucidation of their functions at the biophysical, biochemical, cellular and human level as well as studies revealing novel functions of already known biofactors. The journal encourages the submission of studies that use biochemistry, biophysics, cell and molecular biology and/or cell signaling approaches.
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