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钝叶酸模与精氨酸酶/一氧化氮合酶抑制剂联合使用通过下调氧化应激、炎症和多胺合成发挥抗癌作用。

Anti-cancer effect of Rumex obtusifolius in combination with arginase/nitric oxide synthase inhibitors via downregulation of oxidative stress, inflammation, and polyamine synthesis.

作者信息

Ginovyan Mikayel, Javrushyan Hayarpi, Petrosyan Gayane, Kusznierewicz Barbara, Koss-Mikołajczyk Izabela, Koziara Zuzanna, Kuczyńska Monika, Jakubek Patrycja, Karapetyan Anna, Sahakyan Naira, Maloyan Alina, Bartoszek Agnieszka, Avtandilyan Nikolay

机构信息

Research Institute of Biology, Yerevan State University, Yerevan, Armenia; Department of Biochemistry, Microbiology and Biotechnology, Yerevan State University, Yerevan, Armenia.

Research Institute of Biology, Yerevan State University, Yerevan, Armenia.

出版信息

Int J Biochem Cell Biol. 2023 May;158:106396. doi: 10.1016/j.biocel.2023.106396. Epub 2023 Mar 12.

DOI:10.1016/j.biocel.2023.106396
PMID:36918141
Abstract

Cancer continues to be a leading cause of death worldwide, making the development of new treatment methods crucial in the fight against it. With cancer incidence rates increasing worldwide, ongoing research must focus on identifying new and effective ways to prevent and treat the disease. The combination of herbal extracts with chemotherapeutic agents has gained much interest as a novel strategy to combat cancer. Rumex obtusifolius L. is a wild plant known for its medicinal properties and is widely distributed worldwide. Our preclinical evaluations suggested that R. obtusifolius seed extracts possessed cancer-inhibiting properties and we also evaluated the beneficial effects of the arginase inhibitor NG-hydroxy-nor-L-arginine and nitric oxide inhibitor NG-nitro-L-arginine methyl ester in the treatment of breast cancer. The current study aimed to combine these observations and evaluate the antioxidant and antitumor properties of R. obtusifolius extracts alone and in combination with the arginase and nitric oxide synthase inhibitors. Metabolic characterization of the plant extract using a liquid chromatography/high-resolution mass spectrometry advanced system revealed the presence of 240 phenolic compounds many of which possess anticancer properties, according to the literature. In vitro studies revealed a significant cytotoxic effect of the R. obtusifolius extracts on the human colon (HT29) and breast cancer (MCF-7) cell lines. Thus, a new treatment approach of combining R. obtusifolius bioactive phytochemicals with the arginase and nitric oxide synthase inhibitors NG-nitro-L-arginine methyl ester and/or NG-hydroxy-nor-L-arginine, respectively, was proposed and could potentially be an effective way to treat breast cancer. Indeed, these combinations showed immunostimulatory, antiproliferative, antioxidant, anti-inflammatory, and antiangiogenic properties in a rat breast cancer model.

摘要

癌症仍然是全球主要的死亡原因之一,因此开发新的治疗方法对于抗击癌症至关重要。随着全球癌症发病率的上升,正在进行的研究必须专注于寻找预防和治疗该疾病的新的有效方法。将草药提取物与化疗药物联合使用作为一种对抗癌症的新策略已引起广泛关注。钝叶酸模是一种以其药用特性而闻名的野生植物,在全球广泛分布。我们的临床前评估表明,钝叶酸模种子提取物具有抗癌特性,并且我们还评估了精氨酸酶抑制剂NG-羟基-L-精氨酸和一氧化氮抑制剂NG-硝基-L-精氨酸甲酯在乳腺癌治疗中的有益作用。当前的研究旨在结合这些观察结果,评估钝叶酸模提取物单独以及与精氨酸酶和一氧化氮合酶抑制剂联合使用时的抗氧化和抗肿瘤特性。使用液相色谱/高分辨率质谱先进系统对植物提取物进行代谢表征,结果显示存在240种酚类化合物,根据文献,其中许多具有抗癌特性。体外研究表明,钝叶酸模提取物对人结肠(HT29)和乳腺癌(MCF-7)细胞系具有显著的细胞毒性作用。因此,提出了一种将钝叶酸模生物活性植物化学物质分别与精氨酸酶和一氧化氮合酶抑制剂NG-硝基-L-精氨酸甲酯和/或NG-羟基-L-精氨酸联合使用的新治疗方法,这可能是治疗乳腺癌的有效途径。事实上,这些组合在大鼠乳腺癌模型中显示出免疫刺激、抗增殖、抗氧化、抗炎和抗血管生成特性。

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