关键词: Apoptosis Breast cancer Chemotherapy Nyctanthes arbor-Tristis (L.) flower extract T-cell lymphoma Western blot

Mesh : Animals Plant Extracts / pharmacology therapeutic use Flowers / chemistry Mitochondria / drug effects Female Lymphoma, T-Cell / drug therapy pathology Breast Neoplasms / drug therapy pathology Humans Apoptosis / drug effects Antineoplastic Agents, Phytogenic / pharmacology therapeutic use Mice Adenocarcinoma / drug therapy pathology Mice, Inbred BALB C Cell Line, Tumor Oleaceae / chemistry Reactive Oxygen Species / metabolism Membrane Potential, Mitochondrial / drug effects Cell Proliferation / drug effects Xenograft Model Antitumor Assays

来  源:   DOI:10.1016/j.jep.2024.118537

Abstract:
BACKGROUND: 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.
OBJECTIVE: 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.
METHODS: The ethyl-acetate extract of NAT(L.) was tested against breast cancer cells to assess the anticancer potential. To evaluate apoptosis, intracellular 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.
RESULTS: 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.
CONCLUSIONS: 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.
摘要:
背景:Nyctanthesarbor-tristis的花(L.)治愈口腔溃疡。它的酊剂促进胃分泌物,口服时改善肺部排痰。传统上,它被用来治疗sc疮和其他皮肤问题。NAT的叶子(L.)植物在阿育吠陀医学中用于治疗坐骨神经痛,慢性发热,风湿病,内部蠕虫感染,作为泻药,发汗,和利尿剂.用于治疗蛇咬伤和支气管炎的树皮。除了传统用途,从药理学上讲,这种植物具有有效的抗疟药,抗关节炎,抗癌和抗糖尿病活性。然而,NAT的机制抗增殖潜力(L.)花作为抗癌疗法尚未被探索。
目的:当前的研究基于广泛的科学文献,这些文献强调了NAT的营养和治疗益处(L.).进行了本研究以确定NAT的治疗效果(L.)针对乳腺癌细胞和T细胞淋巴瘤。
方法:NAT的乙酸乙酯提取物(L.)进行了针对乳腺癌细胞的测试,以评估抗癌潜力。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。
结果:我们目前的研究表明NAT(L.)在IC50为320μg/ml时有效地对乳腺癌细胞发挥抗癌活性,而对IC50超过480μg/ml的正常细胞的影响较小。荧光成像显示NAT(L.)处理引起凋亡细胞死亡的浓度依赖性上升,线粒体动力学改变,随后通过流式细胞术证实。Further,流式细胞仪分析描绘了乙酸乙酯花提取物暴露促进细胞停滞在S期的细胞周期。凋亡蛋白如Bax的差异表达,Bcl-2,裂解的PARP-1,裂解的caspase3,细胞色素-c,p53和VEGFA受NAT的影响(L.)治疗。体内抗肿瘤活性研究描述了NAT(L.)治疗可显着增加T细胞淋巴瘤小鼠的寿命,同时减少肿瘤负荷和腹部大小的生长模式,而不会引起明显的其他明显副作用,如组织病理学研究所证明的。
结论:我们目前的发现揭示了NAT(L.)乙酸乙酯花提取物可能诱导线粒体途径凋亡,促进细胞周期停滞,减少小鼠的肿瘤负荷,增强生存能力,可能是对抗三阴性乳腺癌和淋巴瘤的有希望的药物。
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