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探索水溶性南非钩麻提取物作为三阴性乳腺癌转移的治疗方法。

Exploring Water-Soluble South African Harv Extract as a Therapeutic Approach for Triple-Negative Breast Cancer Metastasis.

作者信息

Alaouna Mohammed, Hull Rodney, Molefi Thulo, Khanyile Richard, Mbodi Langanani, Luvhengo Thifhelimbilu Emmanuel, Chauke-Malinga Nkhensani, Phakathi Boitumelo, Penny Clement, Dlamini Zodwa

机构信息

Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2193, South Africa.

SAMRC Precision Oncology Research Unit (PORU), DSI/NRF SARChI Chair in Precision Oncology and Cancer Prevention (POCP), Pan African Cancer Research Institute (PACRI), University of Pretoria, Pretoria 0084, South Africa.

出版信息

Curr Issues Mol Biol. 2024 Sep 26;46(10):10806-10828. doi: 10.3390/cimb46100642.

DOI:10.3390/cimb46100642
PMID:39451522
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11506433/
Abstract

Triple-negative breast cancer (TNBC) accounts for approximately 20% of all breast cancer cases and is characterized by a lack of estrogen, progesterone, and human epidermal growth factor 2 receptors. Current targeted medicines have been unsuccessful due to this absence of hormone receptors. This study explored the efficacy of , a South African medicinal plant, for the treatment of TNBC metastasis. Extracts from leaves were prepared using water and methanol. However, only the water-soluble extract showed anti-cancer activity and the effects of this water-soluble extract on cell adhesion, invasion, and migration, and its antioxidant activity were assessed using MCF-10A and MDA-MB-231 cells. The extract that was soluble in water effectively decreased the movement and penetration of MDA-MB-231 cells through the basement membrane in scratch and invasion tests, while enhancing their attachment to a substance resembling an extracellular matrix. The sample showed mild-to-low antioxidant activity in the antioxidant assy. Nuclear magnetic resonance spectroscopy revealed 61 chemical components in the water-soluble extract, including DDMP, 1,2,4-triazine-3,5(2H,4H)-dione, vanillin, schisandrin, taurolidine, and α-pinene, which are known to have anti-cancer properties. An in-depth examination of the transcriptome showed alterations in genes linked to angiogenesis, metastasis, and proliferation post-treatment, with reduced activity in growth receptor signaling, angiogenesis, and cancer-related pathways, such as the Wnt, Notch, and PI3K pathways. These results indicate that may be a beneficial source of lead chemicals for the development of potential therapeutic medicines that target TNBC metastasis. Additional studies are required to identify the precise bioactive chemical components responsible for the observed anti-cancer effects.

摘要

三阴性乳腺癌(TNBC)约占所有乳腺癌病例的20%,其特征是缺乏雌激素、孕激素和人表皮生长因子2受体。由于缺乏这些激素受体,目前的靶向药物治疗并不成功。本研究探索了一种南非药用植物对TNBC转移的治疗效果。使用水和甲醇制备了该植物叶子的提取物。然而,只有水溶性提取物显示出抗癌活性,并使用MCF-10A和MDA-MB-231细胞评估了这种水溶性提取物对细胞黏附、侵袭和迁移的影响及其抗氧化活性。在划痕和侵袭试验中,该植物的水溶性提取物有效地降低了MDA-MB-231细胞穿过基底膜的运动和穿透能力,同时增强了它们与类似细胞外基质物质的附着。该样品在抗氧化试验中显示出轻度至低度的抗氧化活性。核磁共振光谱分析揭示了水溶性提取物中的61种化学成分,包括已知具有抗癌特性的DDMP、1,2,4-三嗪-3,5(2H,4H)-二酮、香草醛、五味子素、牛磺罗定和α-蒎烯。对转录组的深入研究表明,治疗后与血管生成、转移和增殖相关的基因发生了改变,生长受体信号传导、血管生成以及癌症相关通路(如Wnt、Notch和PI3K通路)的活性降低。这些结果表明,该植物可能是开发针对TNBC转移的潜在治疗药物的有益先导化合物来源。需要进一步的研究来确定导致观察到的抗癌效果的确切生物活性化学成分。

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