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曲克芦丁在三阴性乳腺癌细胞中的增强凋亡作用及癌基因调控机制

Enhanced apoptogenesis and oncogene regulatory mechanism of troxerutin in triple negative breast cancer cells.

作者信息

Saranya Thiruvenkataswamy, Kavithaa Krishnamoorthy, Paulpandi Manickam, Ramya Sennimalai, Preethi Sivashanmugam, Balachandar Vellingiri, Narayanasamy Arul

机构信息

Disease Proteomics Laboratory, Department of Zoology, Bharathiar University, Coimbatore, Tamil Nadu 641 046, India.

Human Molecular Cytogenetics & Stem Cell Laboratory, Department of Human Genetics & Molecular Biology, Bharathiar University, Coimbatore, Tamil Nadu 641 046, India.

出版信息

Toxicol Res (Camb). 2020 May 11;9(3):230-238. doi: 10.1093/toxres/tfaa029. eCollection 2020 Jun.

Abstract

Triple negative breast carcinoma (TNBC) is an aggressive form of cancer, with high rates of morbidity, mortality, poor prognosis and limited therapeutic options. The objective of the present study was to elaborate the anticancer activity of Troxerutin (TXN) in TNBC/MDA-MB-231 cells. Herein, we demonstrated the inhibitory effects of TXN on the breast cancer cell growth via induction of apoptosis. Mitochondrial membrane potential (∆Ψm), DNA damage and apoptotic nuclear changes were analyzed by flowcytometry, AO/EtBr and Hoechst staining, respectively. Furthermore, apoptotic protein and gene expressions were analyzed by western blot and reverse transcription polymerase chain reaction (RT-PCR), respectively. Our results indicated that TXN induces apoptosis as evidenced by inhibit the cell proliferation, enhanced apoptotic activation, altered mitochondrial membrane potential and elevated level of DNA damage in TNBC cells. Furthermore, the TXN inhibit anti-apoptotic protein expression with the subsequent upregulation of Cytochrome c, Caspase-9 and Caspase-3. Thus, TXN induces apoptosis in TNBC cells through inducing nuclear damage and altered apoptotic marker expressions. Therefore, TXN might be used as a potential therapeutic agent for the treatment of triple negative breast cancer.

摘要

三阴性乳腺癌(TNBC)是一种侵袭性癌症,发病率和死亡率高,预后较差且治疗选择有限。本研究的目的是阐述曲克芦丁(TXN)对TNBC/MDA-MB-231细胞的抗癌活性。在此,我们证明了TXN通过诱导凋亡对乳腺癌细胞生长具有抑制作用。分别通过流式细胞术、AO/EtBr染色和Hoechst染色分析线粒体膜电位(∆Ψm)、DNA损伤和凋亡核变化。此外,分别通过蛋白质印迹法和逆转录聚合酶链反应(RT-PCR)分析凋亡蛋白和基因表达。我们的结果表明,TXN可诱导凋亡,表现为抑制TNBC细胞的增殖、增强凋亡激活、改变线粒体膜电位以及提高DNA损伤水平。此外,TXN抑制抗凋亡蛋白表达,随后上调细胞色素c、半胱天冬酶-9和半胱天冬酶-3。因此,TXN通过诱导核损伤和改变凋亡标志物表达来诱导TNBC细胞凋亡。所以,TXN可能用作治疗三阴性乳腺癌的潜在治疗药物。

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