Genistein enhances TLR3-mediated apoptosis and immune signaling in breast cancer cells.

IF 3.5 4区 医学 Q2 ONCOLOGY
Suleyman Kaleli, Asuman Deveci Ozkan, Gamze Guney Eskiler, Kaan Furkan Hamarat, Rabia Rana Derlioglu, Sevinc Yanar, Ecir Ali Cakmak
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引用次数: 0

Abstract

Breast cancer is one of the most common malignant tumors globally and the second leading cause of cancer-related death in women. Toll-like receptors (TLR) constitute a family of transmembrane receptors playing a crucial role in innate immunity. TLR3 is a type of TLR that is activated following Poly (I:C) double-stranded RNA binding. TLR3 activation leads to tumor suppression, and TLR3 directly causes apoptotic effects in cancer cells. Genistein (GEN), a phytoestrogen found in soy, inhibits cellular proliferation, induces apoptosis, and arrests the cell cycle. Therefore, it is important to determine the roles of immunotherapeutic agents targeting TLR3 in cancer treatment. The study aimed to determine the anti-inflammatory effect of GEN on breast cancer cells for the first time. The anti-inflammatory effects of GEN on the TLR3 signaling pathway were evaluated using Annexin V and cell cycle analysis, immunofluorescence assay, acridine orange staining, Western blotting, and ELISA cytokine release level in MCF-7 (hormone-dependent) and MDA-MB-231 (triple negative) breast cancer cells. The GEN alone treatment increased apoptosis, cell cycle arrest, apoptotic cell morphology, and the expression of TLR3, IRF3, AP-1, and p-NF-kB proteins. Additionally, higher levels of INF-β and TNF-α in both cells compared to treatment with Poly I:C alone were detected. These effects were more pronounced in MCF-7 cells than in MDA-MB-231 cells. Stimulation of the TLR3 signaling pathway was enhanced in the presence of GEN, leading to increased apoptosis.

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染料木素增强tlr3介导的乳腺癌细胞凋亡和免疫信号传导。
乳腺癌是全球最常见的恶性肿瘤之一,也是妇女癌症相关死亡的第二大原因。toll样受体(TLR)是一个跨膜受体家族,在先天免疫中起着至关重要的作用。TLR3是一种在Poly (I:C)双链RNA结合后被激活的TLR。TLR3的激活导致肿瘤抑制,TLR3直接导致癌细胞的凋亡作用。染料木素(GEN)是一种在大豆中发现的植物雌激素,可抑制细胞增殖,诱导细胞凋亡,并延缓细胞周期。因此,确定靶向TLR3的免疫治疗剂在癌症治疗中的作用是非常重要的。本研究旨在首次确定GEN对乳腺癌细胞的抗炎作用。在MCF-7(激素依赖性)和MDA-MB-231(三阴性)乳腺癌细胞中,采用Annexin V和细胞周期分析、免疫荧光法、吖胺橙染色、Western blotting和ELISA检测细胞因子释放水平,评估GEN对TLR3信号通路的抗炎作用。单独使用GEN可增加细胞凋亡、细胞周期阻滞、凋亡细胞形态以及TLR3、IRF3、AP-1和p-NF-kB蛋白的表达。此外,与单独使用Poly I:C相比,两种细胞中检测到更高水平的INF-β和TNF-α。这些作用在MCF-7细胞中比在MDA-MB-231细胞中更为明显。GEN的存在增强了TLR3信号通路的刺激,导致细胞凋亡增加。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Medical Oncology
Medical Oncology 医学-肿瘤学
CiteScore
4.20
自引率
2.90%
发文量
259
审稿时长
1.4 months
期刊介绍: Medical Oncology (MO) communicates the results of clinical and experimental research in oncology and hematology, particularly experimental therapeutics within the fields of immunotherapy and chemotherapy. It also provides state-of-the-art reviews on clinical and experimental therapies. Topics covered include immunobiology, pathogenesis, and treatment of malignant tumors.
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