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Nyctanthes arbor-tristis (L.) 花提取物对乳腺癌和 T 细胞淋巴瘤的线粒体介导抑制作用:体外和体内研究。

Mitochondria mediated inhibitory effect of Nyctanthes arbor-tristis (L.) flower extract against breast adenocarcinoma and T-cell lymphoma: an in vitro and in vivo study.

发表日期:2024 Jul 09
作者: Pooja Goswami, Virendra Singh, Biplob Koch
来源: JOURNAL OF ETHNOPHARMACOLOGY

摘要:

Nyctanthes arbor-tristis (L.) 的花可治愈口腔溃疡。口服其酊剂可促进胃液分泌,并改善肺部排痰。传统上它被用来治疗疥疮和其他皮肤问题。 NAT(L.) 植物的叶子在阿育吠陀医学中用于治疗坐骨神经痛、慢性发烧、风湿病、体内蠕虫感染,并用作泻药、发汗剂和利尿剂。树皮用于治疗蛇咬伤和支气管炎。除了传统用途外,这种植物在药理学上还具有有效的抗疟疾、抗关节炎、抗癌和抗糖尿病活性。然而,NAT(L.) 花作为抗癌疗法的抗增殖潜力尚未得到探索。当前的研究基于广泛的科学文献,强调了 NAT(L.) 的营养和治疗益处。目前的研究是为了确定 NAT(L.) 对乳腺癌细胞和 T 细胞淋巴瘤的治疗效果。对 NAT(L.) 的乙酸乙酯提取物进行了针对乳腺癌细胞的测试,以评估其抗癌潜力。为了评估细胞凋亡、ROS 水平和线粒体动力学,采用荧光显微镜和流式细胞术。此外,还进行了细胞周期分析和蛋白质印迹。此外,在携带 T 细胞淋巴瘤的 BALB/c 小鼠模型中研究了花提取物的体内抗肿瘤功效。我们目前的研究表明,NAT (L.) 在 IC50 320 μg/ml 时对乳腺癌细胞有效发挥抗癌活性,同时具有对正常细胞影响较小,IC50大于480 μg/ml。荧光成像显示,NAT (L.) 治疗会引起凋亡细胞死亡发生率呈浓度依赖性上升,并改变线粒体动力学,随后通过流式细胞术证实。此外,流式细胞术分析表明,暴露于乙酸乙酯花提取物会促进细胞停滞在细胞周期的 S 期。 Bax、Bcl-2、cleaved PARP-1、cleaved caspase 3、细胞色素-c、p53 和 VEGF A 等凋亡蛋白的差异表达受到 NAT (L.) 处理的影响。体内抗肿瘤活性研究表明,NAT(L.) 疗法显着延长了携带 T 细胞淋巴瘤的小鼠的寿命,同时减少了肿瘤负荷和腹部大小生长模式,并且不会引起组织病理学研究所证明的显着其他明显副作用。研究结果表明,NAT(L.) 醋酸乙酯花提取物可能诱导线粒体凋亡途径,促进细胞周期停滞,减少小鼠肿瘤负荷,提高生存能力,并可能成为对抗三阴性乳腺癌和淋巴瘤的有前途的药物。版权所有 © 2024爱思唯尔 B.V. 出版
The flowers of Nyctanthes arbor-tristis (L.) heals mouth ulcers. Its tinctures promote gastric secretions, and improve lung expectoration when taken orally. It has traditionally been used to treats scabies and other skin problems. The leaves of NAT(L.) plant are used in Ayurvedic medicine to treat sciatica, chronic fever, rheumatism, internal worm infections, and as a laxative, diaphoretic, and diuretic. The bark used in treatment of snakebite and bronchitis. In addition to traditional uses, pharmacologically this plant has potent antimalarial, antiarthritic, anticancer and antidiabetic activity. However, the mechanistic antiproliferative potentials of NAT(L.) flower as anticancer therapeutics has not yet been explored.The current study is based on a broad range of scientific literature that highlights the nutritional and therapeutic benefits of NAT (L.). Present investigation was carried out to determine the therapeutic efficacy of NAT (L.) against breast adenocarcinoma cells and T-cell lymphoma.The ethyl-acetate extract of NAT(L.) was tested against breast cancer cells to assess the anticancer potential. To evaluate Apoptosis, ROS levels and mitochondrial dynamics, fluorescence microscopy and flow cytometry were employed. Additionally, cell cycle analysis and western blotting were also performed. Furthermore, in vivo antitumor efficacy of flower extracts was investigated in T-cell lymphoma-bearing BALB/c mice model.Our present study revealed that NAT (L.) exert anticancer activity against breast cancer cells effectively at IC50 320 μg/ml while having less impact on normal cells with IC50 more than 480 μg/ml. Fluorescence imaging showed that NAT (L.) treatment elicits a concentration-dependent rise in the occurrence of apoptotic cell deaths with altered mitochondrial dynamics and was subsequently confirmed by flow cytometry. Further, flow cytometric analysis delineates ethyl acetate flower extract exposure promotes arrest of cells in S phase of the cell cycle. The differential expression of apoptotic proteins such as Bax, Bcl-2, cleaved PARP-1, cleaved caspase 3, Cytochrome-c, p53 and VEGF A were influenced by NAT (L.) treatment. The in vivo antitumor activity study delineates that NAT(L.) therapy significantly increased the life span of T-cell lymphoma bearing mice while reducing tumor load and belly size growth pattern without causing significant other distinct side effects as evident by histopathological studies.Our current findings unveil that NAT(L.) ethyl acetate flower extract potentially induces mitochondrial pathway of apoptosis, promote cell cycle arrest, reduces tumor load of mice, enhances survivability and could be a promising agent against the triple negative breast cancer and lymphoma.Copyright © 2024. Published by Elsevier B.V.