化学预防剂姜黄素类似物1.1促进TNBC MDA-MB-231和HER2阳性HCC1954细胞的中期阻滞并增强细胞内活性氧化物水平。
Chemoprevention curcumin analog 1.1 promotes metaphase arrest and enhances intracellular reactive oxygen species levels on TNBC MDA-MB-231 and HER2-positive HCC1954 cells.
发表日期：2023
作者：
Dhania Novitasari, Riris Istighfari Jenie, Jun-Ya Kato, Edy Meiyanto
来源：
Cell Death & Disease
摘要：
先前的研究指出，化学预防剂姜黄素类似物-1.1（CCA-1.1）展示了对乳腺癌、白血病和结直肠癌细胞的抗肿瘤作用。通过利用MDA-MB-231和HCC1954细胞系，我们评估了CCA-1.1的抗癌特性及其促进细胞死亡的介导活性。使用尝试蓝排除法对细胞毒性和抗增殖活性进行了检测。通过流式细胞术建立了CCA-1.1处理后的细胞周期分布情况。使用May-Grünwald-Giemsa和Hoechst染色来确定CCA-1.1处理后的细胞周期阻滞情况。通过免疫印迹法研究了CCA-1.1对有丝分裂激酶（Aurora A、p-Aurora A、p-PLK1和p-cyclin B1）表达的影响。使用X-gal溶液染色来观察CCA-1.1对细胞衰老的影响。通过DCFDA测定法和线粒体耗氧速率来评估ROS水平和线粒体呼吸能力。CCA-1.1表现出细胞毒性活性并抑制细胞增殖，具有不可逆的效果，流式细胞术分析表明CCA-1.1显著阻滞了G2/M期间，进一步评估发现CCA-1.1引起了中期阻滞。免疫印迹实验证实CCA-1.1抑制了MDA-MB-231细胞中的Aurora A激酶活性。CCA-1.1处理后细胞中ROS水平升高，这可能促进细胞衰老并抑制MDA-MB-231细胞的基础线粒体呼吸。我们的数据表明，该研究在体外证明了CCA-1.1参与细胞周期调控和ROS生成作为抑制乳腺癌细胞生长的因素的概念证明。版权所有：© 2023 Research in Pharmaceutical Sciences.
Previous studies highlighted that chemoprevention curcumin analog-1.1 (CCA-1.1) demonstrated an antitumor effect on breast, leukemia, and colorectal cancer cells. By utilizing immortalized MDA-MB-231 and HCC1954 cells, we evaluated the anticancer properties of CCA-1.1 and its mediated activity to promote cellular death.Cytotoxicity and anti-proliferation were assayed using trypan blue exclusion. The cell cycle profile after CCA-1.1 treatment was established through flow cytometry. May-Grünwald-Giemsa and Hoechst staining were performed to determine the cell cycle arrest upon CCA-1.1 treatment. The involvement of CCA-1.1 in mitotic kinases (aurora A, p-aurora A, p-PLK1, and p-cyclin B1) expression was investigated by immunoblotting. CCA-1.1-treated cells were stained with the X-gal solution to examine the effect on senescence. ROS level and mitochondrial respiration were assessed by DCFDA assay and mitochondrial oxygen consumption rate, respectively.CCA-1.1 exerted cytotoxic activity and inhibited cell proliferation with an irreversible effect, and the flow cytometry analysis demonstrated that CCA-1.1 significantly halted during the G2/M phase, and further assessment revealed that CCA-1.1 caused metaphase arrest. Immunoblot assays confirmed CCA-1.1 suppressed aurora A kinase in MDA-MB-231 cells. The ROS level was elevated after treatment with CCA-1.1, which might promote cellular senescence and suppress basal mitochondrial respiration in MDA-MB-231 cells.Our data suggested the in vitro proof-of-concept that supports the involvement in cell cycle regulation and ROS generation as contributors to the effectiveness of CCA-1.1 in suppressing breast cancer cell growth.Copyright: © 2023 Research in Pharmaceutical Sciences.