Faculty of Medicine, Department of Biophysics, Erciyes University, Kayseri, Turkey.
Genom and Stem Cell Center, Erciyes University, Kayseri, Turkey.
J Membr Biol. 2022 Feb;255(1):33-39. doi: 10.1007/s00232-021-00201-1. Epub 2021 Sep 27.
Cyclosporine A (CsA) is an immunosuppressive drug commonly used to prevent autoimmune diseases. At the same time, CsA is a calcineurin (CaN) inhibitor. It affects the intracellular calcium signaling pathway. The effect of CsA on breast cancer cells, MDA-MB-231, plasma membrane calcium pump 1 (PMCA1), calmodulin (CaM), calcineurin (CaN), and cMyc, which are proteins that affect calcium signaling, were investigated. CsA inhibited the proliferation of MDA-MB-231 cells but did not affect the migration of the cells. After 24 h of incubation, CsA suppressed the PMCA1 protein, which pumps intracellular calcium out of the cell. At the same time, calcium started to accumulate inside the cell and CaM protein was expressed, while PMCA1 was suppressed. The CaN protein was suppressed 72 h after the administration of CsA, but the cMyc protein was expressed. Interestingly, 24 h incubation when the PMCA1 protein is down-regulated after the duration of time, the cMyc protein is also down-regulated. Although the indirect effect of CaN and cMyc is known, this relationship between PMCA1 and cMyc was not known. As a result, it has been shown that CsA affects the PMCA pump by disrupting the intracellular calcium pathway in breast cancer cells.
环孢素 A(CsA)是一种常用的免疫抑制剂,用于预防自身免疫性疾病。同时,CsA 也是一种钙调神经磷酸酶(CaN)抑制剂。它影响细胞内钙信号通路。研究了 CsA 对乳腺癌细胞 MDA-MB-231、质膜钙泵 1(PMCA1)、钙调蛋白(CaM)、钙调神经磷酸酶(CaN)和 cMyc 的影响,这些蛋白均影响钙信号。CsA 抑制 MDA-MB-231 细胞的增殖,但不影响细胞的迁移。孵育 24 小时后,CsA 抑制将细胞内钙泵出细胞的 PMCA1 蛋白。同时,钙开始在细胞内积累,CaM 蛋白表达,而 PMCA1 被抑制。CsA 给药 72 小时后,CaN 蛋白被抑制,但 cMyc 蛋白表达。有趣的是,24 小时孵育后,PMCA1 蛋白下调持续时间后,cMyc 蛋白也下调。虽然已知 CaN 和 cMyc 的间接作用,但 PMCA1 和 cMyc 之间的这种关系尚不清楚。因此,结果表明 CsA 通过破坏乳腺癌细胞内的细胞内钙途径来影响 PMCA 泵。