L. Babich, S. Shlykov, O. Yesypenko, A. O. Bavelska-Somak, A. G. Zahoruiko, I. Horak, L. Drobot, S. Kosterin
{"title":"杯[4]芳烃查尔酮酰胺C-1011对适配蛋白Ruk/CIN85表达水平不同的4T1小鼠乳腺腺癌细胞的生存能力有不同的影响","authors":"L. Babich, S. Shlykov, O. Yesypenko, A. O. Bavelska-Somak, A. G. Zahoruiko, I. Horak, L. Drobot, S. Kosterin","doi":"10.15407/ubj94.02.024","DOIUrl":null,"url":null,"abstract":"According to our earlier data, calix[4]arene chalcone amides modulate Ca ions exchange in the myometrium mitochondria and the level of inner membrane polarization that can potentially affect cell survival. To test this hypothesis, we studied the effect of calix[4]arene with 4 chalcone amide groups on mitochondria membrane polarization and viability of 4T1 mouse breast adenocarcinoma cells, a surrogate model of human triple-negative breast cancer, and on its highly malignant subline overexpressing the adaptor protein Ruk/CIN85. Mitochondria membrane potential was measured by flow cytometry, and cell viability was assessed using Trypan blue dye exclusion. It was shown that mitochondrial membranes of control (Mock) cells had a higher polarization level (67.80 ± 8.82 r.u., n = 5) compared to 4T1 cells with up-regulation of Ruk/CIN85 (RukUp cells) (25.42 ± 2.58 r.u., n = 4). Upon incubation of cells with 1 μM calix[4]arene C-1011, the CCCP-sensitive component of mitochondrial membranes polarization decreased (by almost 50%) in 4T1 Mock cells and did not change in RukUp cells compared with the control. It was demonstrated that 1 μM calix[4]arene C-1011 suppressed the viability of 4T1 Mock cells by 45%, but did not affect RukUp cells considerably. It was suggested that calix[4]arene chalcone amide С-1011 decreased mouse breast adenocarcinoma 4T1 cell viability at least by affecting mitochondrial membrane polarization.The data obtained indicate the prospects of further studies of calix[4]arene chalcone amide as a potential anticancer drug candidate.","PeriodicalId":23007,"journal":{"name":"The Ukrainian Biochemical Journal","volume":"14 1","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2022-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Calix[4]arene chalcone amide C-1011 elicits differential effects on the viability of 4T1 mouse breast adenocarcinoma cells with different levels of adaptor protein Ruk/CIN85 expression\",\"authors\":\"L. Babich, S. Shlykov, O. Yesypenko, A. O. Bavelska-Somak, A. G. Zahoruiko, I. Horak, L. Drobot, S. 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Upon incubation of cells with 1 μM calix[4]arene C-1011, the CCCP-sensitive component of mitochondrial membranes polarization decreased (by almost 50%) in 4T1 Mock cells and did not change in RukUp cells compared with the control. It was demonstrated that 1 μM calix[4]arene C-1011 suppressed the viability of 4T1 Mock cells by 45%, but did not affect RukUp cells considerably. 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引用次数: 0
摘要
根据我们早期的数据,杯[4]芳烃查尔酮酰胺调节肌层线粒体中的钙离子交换和内膜极化水平,这可能会影响细胞存活。为了验证这一假设,我们研究了带有4个查尔酮酰胺基团的杯[4]芳烯对人类三阴性乳腺癌替代模型4T1小鼠乳腺腺癌细胞线粒体膜极化和活力的影响,以及对其高恶性亚群过表达适配蛋白Ruk/CIN85的影响。流式细胞术测定线粒体膜电位,台盼蓝染色法测定细胞活力。结果表明,对照(Mock)细胞的线粒体膜极化水平(67.80±8.82 r.u, n = 5)高于4T1细胞,RukUp细胞的Ruk/CIN85表达上调(25.42±2.58 r.u, n = 4)。1 μM杯[4]烯C-1011孵育后,4T1模拟细胞的cccp敏感成分线粒体膜极化水平下降(近50%),而RukUp细胞的cccp敏感成分与对照相比没有变化。结果表明,1 μM杯[4]芳烃C-1011对4T1模拟细胞的活性有45%的抑制作用,但对RukUp细胞没有明显影响。研究表明,杯[4]芳烃查尔酮酰胺С-1011至少通过影响线粒体膜极化降低小鼠乳腺腺癌4T1细胞活力。这些数据表明了杯[4]芳烃查尔酮酰胺作为潜在的抗癌候选药物的进一步研究前景。
Calix[4]arene chalcone amide C-1011 elicits differential effects on the viability of 4T1 mouse breast adenocarcinoma cells with different levels of adaptor protein Ruk/CIN85 expression
According to our earlier data, calix[4]arene chalcone amides modulate Ca ions exchange in the myometrium mitochondria and the level of inner membrane polarization that can potentially affect cell survival. To test this hypothesis, we studied the effect of calix[4]arene with 4 chalcone amide groups on mitochondria membrane polarization and viability of 4T1 mouse breast adenocarcinoma cells, a surrogate model of human triple-negative breast cancer, and on its highly malignant subline overexpressing the adaptor protein Ruk/CIN85. Mitochondria membrane potential was measured by flow cytometry, and cell viability was assessed using Trypan blue dye exclusion. It was shown that mitochondrial membranes of control (Mock) cells had a higher polarization level (67.80 ± 8.82 r.u., n = 5) compared to 4T1 cells with up-regulation of Ruk/CIN85 (RukUp cells) (25.42 ± 2.58 r.u., n = 4). Upon incubation of cells with 1 μM calix[4]arene C-1011, the CCCP-sensitive component of mitochondrial membranes polarization decreased (by almost 50%) in 4T1 Mock cells and did not change in RukUp cells compared with the control. It was demonstrated that 1 μM calix[4]arene C-1011 suppressed the viability of 4T1 Mock cells by 45%, but did not affect RukUp cells considerably. It was suggested that calix[4]arene chalcone amide С-1011 decreased mouse breast adenocarcinoma 4T1 cell viability at least by affecting mitochondrial membrane polarization.The data obtained indicate the prospects of further studies of calix[4]arene chalcone amide as a potential anticancer drug candidate.