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冷等离体子体引发黑素瘤细胞钙离子内流,触发 CAP 诱导的衰老。

Cold atmospheric plasma causes a calcium influx in melanoma cells triggering CAP-induced senescence.

机构信息

Institute of Biochemistry, Emil-Fischer-Center, University of Erlangen-Nürnberg, Erlangen, Germany.

Institute of Physiology and Pathophysiology, University of Erlangen-Nürnberg, Erlangen, Germany.

出版信息

Sci Rep. 2018 Jul 3;8(1):10048. doi: 10.1038/s41598-018-28443-5.

DOI:10.1038/s41598-018-28443-5
PMID:29968804
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6030087/
Abstract

Cold atmospheric plasma (CAP) is a promising approach in anti-cancer therapy, eliminating cancer cells with high selectivity. However, the molecular mechanisms of CAP action are poorly understood. In this study, we investigated CAP effects on calcium homeostasis in melanoma cells. We observed increased cytoplasmic calcium after CAP treatment, which also occurred in the absence of extracellular calcium, indicating the majority of the calcium increase originates from intracellular stores. Application of previously CAP-exposed extracellular solutions also induced cytoplasmic calcium elevations. A substantial fraction of this effect remained when the application was delayed for one hour, indicating the chemical stability of the activating agent(s). Addition of ryanodine and cyclosporin A indicate the involvement of the endoplasmatic reticulum and the mitochondria. Inhibition of the cytoplasmic calcium elevation by the intracellular chelator BAPTA blocked CAP-induced senescence. This finding helps to understand the molecular influence and the mode of action of CAP on tumor cells.

摘要

冷等离体子体(CAP)是一种有前途的抗癌治疗方法,具有高选择性地消除癌细胞的特点。然而,CAP 的作用机制尚不清楚。在这项研究中,我们研究了 CAP 对黑素瘤细胞钙稳态的影响。我们观察到 CAP 处理后细胞质钙增加,即使在没有细胞外钙的情况下也会发生,这表明钙的增加主要来自细胞内储存。先前暴露于 CAP 的细胞外溶液的应用也会诱导细胞质钙的升高。当应用延迟一小时时,这种效应的很大一部分仍然存在,表明激活剂的化学稳定性。添加 Ryanodine 和环孢菌素 A 表明内质网和线粒体的参与。细胞质钙升高的抑制通过细胞内螯合剂 BAPTA 阻断了 CAP 诱导的衰老。这一发现有助于理解 CAP 对肿瘤细胞的分子影响和作用模式。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c6e/6030087/4e2e085e13da/41598_2018_28443_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c6e/6030087/ea52676f52cd/41598_2018_28443_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c6e/6030087/609eba077383/41598_2018_28443_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c6e/6030087/3ead81cc61e6/41598_2018_28443_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c6e/6030087/7e62da8a0a4a/41598_2018_28443_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c6e/6030087/4e2e085e13da/41598_2018_28443_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c6e/6030087/ea52676f52cd/41598_2018_28443_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c6e/6030087/609eba077383/41598_2018_28443_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c6e/6030087/3ead81cc61e6/41598_2018_28443_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c6e/6030087/7e62da8a0a4a/41598_2018_28443_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c6e/6030087/4e2e085e13da/41598_2018_28443_Fig5_HTML.jpg

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