Pharmacokinetic investigation on the mechanism of interaction of anti-breast cancer calycosin with albumin: In vitro
Pharmacokinetic investigation on the mechanism of interaction of anti-breast cancer calycosin with albumin: In vitro
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DOI：
10.1016/j.arabjc.2023.105175
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发表时间：
2023-08-11
影响因子：
6
通讯作者：
Zhang，Jin
中科院分区：
文献类型：
--
作者：
Fang，Xuan;Li，Jun;Zhang，Jin
有文献表明，毛蕊异黄酮在体外对多种癌细胞具有抗癌作用。然而，基于其与白蛋白作为主要载体蛋白相互作用的毛蕊异黄酮的药代动力学特征以及相应的抗癌机制在很大程度上仍然未知。在此，我们通过广泛收集光谱和理论数据来探讨毛蕊异黄酮与人血清白蛋白（HSA）的相互作用。此外，通过细胞活力、乳酸脱氢酶（LDH）、caspase-3活性和实时PCR检测，探讨了毛蕊异黄酮对乳腺癌细胞MDA-MB 231的抗癌作用。研究结果表明，毛蕊异黄酮与HSA相互作用的猝灭过程基本上是静态的，毛蕊异黄酮-HSA体系是自发形成的。细胞和分子研究表明，毛蕊异黄酮对正常人乳腺上皮细胞（MCF-10A）的活性没有显著的细胞毒性作用，即使在200 μM浓度下，它也能抑制乳腺癌MDA-MB 231细胞的增殖达50%。随后，揭示毛萼异黄酮可通过过表达caspase-3 mRNA、下调Bcl-2、下调mTOR和Akt mRNA介导的caspase-3 mRNA和活性升高，破坏MDA-MB 231细胞的膜完整性，诱导细胞凋亡。因此，我们认识到在乳腺癌MDA-MB 231细胞中，毛蕊异黄酮能够通过凋亡抑制细胞增殖，而凋亡是由Akt/mTOR信号级联控制的。
It has been documented that calycosin induces anticancer effects against a wide range of cancer cells,in vitro. However, pharmacokinetic characteristics of calycosin based on its interaction with albumin as a main carrier protein as well as corresponding anticancer mechanisms remain largely unknown. Herein, we inquired into the interaction of calycosin with human serum albumin (HSA) by a wide range collection of spectroscopic and theoretical data. Also, anticancer effects of calycosin on breast cancer cells, MDA-MB 231, were explored by cell viability, lactate dehydrogenase (LDH), caspase-3 activity, and real-time PCR assays. The findings demonstrated that the quenching process resulting from the interaction of calycosin and HSA was largely static in nature and that the calycosin-HSA system spontaneously forms. Cellular and molecular studies revealed that calycosin did not induce a significant cytotoxic effect on the viability of normal human breast epithelial cells, (MCF-10A), even at 200 μM concentration at which it was able to inhibit the proliferation of breast cancer MDA-MB 231 cells up to 50%. Then, it was disclosed that calycosin can disrupt the membrane integrity and induces apoptosis in MDA-MB 231 cells through overexpression of caspase-3 mRNA, down regulation of Bcl-2, and elevation of caspase-3 mRNA and activity mediated by downregulation of mTOR and Akt mRNA. Therefore, it was realized that in breast cancer MDA-MB 231 cells, calycosin is able to suppress cellular proliferation via apoptosis, which is controlled by the Akt/mTOR signaling cascade.