The recovery from taxane mediated apoptosis in PC-3 castration-resistant metastatic prostate cancer cells

IF 2.6 3区医学 Q3 TOXICOLOGY

Toxicology in Vitro Pub Date : 2024-07-10 DOI:10.1016/j.tiv.2024.105894

Gamze Guney Eskiler , Asuman Deveci Ozkan , Merve Acikel Elmas , Melek Ozturk , Serap Arbak

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引用次数: 0

Abstract

Here, we revealed the reversibility of cabazitaxel (CBZ)-induced apoptosis in PC-3 castration resistant metastatic prostate cancer cells (mCRPC) through the hallmarks of apoptosis. The recovery of PC-3 cells from apoptosis upon removal of CBZ at different recovery periods was evaluated by Annexin V, DNA damage, oxidative damage, mitochondrial membrane depolarization, and caspase activation. Our results showed that the administration of CBZ caused apoptosis for 72 h in PC-3 cells. However, recovered cells exhibited decreased nuclear damage, plasma membrane disruption, ROS level, release cytochrome c level and caspase-3 activation with upregulation of Bcl-2 expression upon removal of especially 1 nM CBZ for 24 h recovery period in PC-3 cells. Our study indicates that CBZ treated PC-3 cells can recover after apoptotic cell death. However, advanced molecular analysis should elucidate the relationship between the molecular mechanisms of recovery and taxane response or resistance in PC-3 mCRPC cells.

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PC-3 耐阉割转移性前列腺癌细胞从紫杉类药物介导的凋亡中恢复。

在这里，我们通过细胞凋亡的标志揭示了卡巴他赛（CBZ）诱导的PC-3阉割耐药转移性前列腺癌细胞（mCRPC）凋亡的可逆性。我们通过Annexin V、DNA损伤、氧化损伤、线粒体膜去极化和caspase活化等指标评估了PC-3细胞在不同恢复期去除CBZ后的凋亡恢复情况。结果表明，服用 CBZ 72 小时后，PC-3 细胞出现凋亡。然而，PC-3细胞在去除特别是1 nM CBZ 24小时恢复期后，恢复细胞的核损伤、质膜破坏、ROS水平、细胞色素c释放水平和caspase-3活化均有所下降，Bcl-2表达上调。我们的研究表明，CBZ 处理的 PC-3 细胞在细胞凋亡后可以恢复。不过，先进的分子分析应能阐明PC-3 mCRPC细胞的恢复与紫杉类药物反应或耐药性之间的关系。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Toxicology in Vitro 医学-毒理学

CiteScore

6.50

自引率

3.10%

发文量

181

审稿时长

65 days

期刊介绍： Toxicology in Vitro publishes original research papers and reviews on the application and use of in vitro systems for assessing or predicting the toxic effects of chemicals and elucidating their mechanisms of action. These in vitro techniques include utilizing cell or tissue cultures, isolated cells, tissue slices, subcellular fractions, transgenic cell cultures, and cells from transgenic organisms, as well as in silico modelling. The Journal will focus on investigations that involve the development and validation of new in vitro methods, e.g. for prediction of toxic effects based on traditional and in silico modelling; on the use of methods in high-throughput toxicology and pharmacology; elucidation of mechanisms of toxic action; the application of genomics, transcriptomics and proteomics in toxicology, as well as on comparative studies that characterise the relationship between in vitro and in vivo findings. The Journal strongly encourages the submission of manuscripts that focus on the development of in vitro methods, their practical applications and regulatory use (e.g. in the areas of food components cosmetics, pharmaceuticals, pesticides, and industrial chemicals). Toxicology in Vitro discourages papers that record reporting on toxicological effects from materials, such as plant extracts or herbal medicines, that have not been chemically characterized.