Methanolic Extracts of D. viscosa Specifically Affect the Cytoskeleton and Exert an Antiproliferative Effect on Human Colorectal Cancer Cell Lines, According to Their Proliferation Rate.

Methanolic Extracts of D. viscosa Specifically Affect the Cytoskeleton and Exert an Antiproliferative Effect on Human Colorectal Cancer Cell Lines, According to Their Proliferation Rate.
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DOI:
10.3390/ijms241914920
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发表时间:
2023-10-05
影响因子:
5.6
通讯作者:
Di Sansebastiano GP
Di Sansebastiano GP
中科院分区:
生物学2区
文献类型:
--
作者:
Anglana C;Rojas M;Girelli CR;Barozzi F;Quiroz-Troncoso J;Alegría-Aravena N;Montefusco A;Durante M;Fanizzi FP;Ramírez-Castillejo C;Di Sansebastiano GP

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大量的研究报道了粘胶dick trichia viscosa (D. viscosa)的药理作用,包括抗氧化、细胞毒性、抗增殖和抗癌特性。在我们的研究中,我们的主要目标是验证一种旨在确定最有效的抗增殖和抗癌作用的部分的预筛选方法。具体来说,我们使用涉及转基因植物的筛选方法研究了不同提取物组分对细胞骨架的影响。肿瘤本质上是异质性的,细胞骨架的成分,特别是微管蛋白,被认为是抗肿瘤药物的战略靶点。为了考虑异质性,我们使用了不同种类的结直肠癌,特别是一种最常见的癌症,而不考虑性别。在有转移的患者中,化疗的有效性受到严重副作用和耐药性的限制。因此需要额外的治疗和抗增殖分子。在我们的研究中,我们使用了以胃肠道分化标记表达为特征的结肠样细胞系(如HT-29细胞系)和未分化的细胞系(如dpd -1、SW480和SW620细胞系),这些细胞系表现出对上皮-间质转化和tgf - β信号的积极调节。我们发现所有三种粘胶提取物都具有抗增殖作用,但对转基因植物的预筛选预计甲醇部分可能是最有希望的,它专门针对细胞骨架并且可能产生较少的副作用。在这里,我们表明在表达亚细胞标记的转基因植物中初步使用筛选可以显著降低成本,并将高级表征集中在最有希望的治疗分子上。
Numerous studies have reported the pharmacological effects exhibited by Dittrichia viscosa, (D. viscosa) including antioxidant, cytotoxic, antiproliferative, and anticancer properties. In our research, our primary objective was to validate a prescreening methodology aimed at identifying the fraction that demonstrates the most potent antiproliferative and anticancer effects. Specifically, we investigated the impact of various extract fractions on the cytoskeleton using a screening method involving transgenic plants. Tumors are inherently heterogeneous, and the components of the cytoskeleton, particularly tubulin, are considered a strategic target for antitumor agents. To take heterogeneity into account, we used different lines of colorectal cancer, specifically one of the most common cancers regardless of gender. In patients with metastasis, the effectiveness of chemotherapy has been limited by severe side effects and by the development of resistance. Additional therapies and antiproliferative molecules are therefore needed. In our study, we used colon-like cell lines characterized by the expression of gastrointestinal differentiation markers (such as the HT-29 cell line) and undifferentiated cell lines showing the positive regulation of epithelial–mesenchymal transition and TGFβ signatures (such as the DLD-1, SW480, and SW620 cell lines). We showed that all three of the D. viscosa extract fractions have an antiproliferative effect but the pre-screening on transgenic plants anticipated that the methanolic fraction may be the most promising, targeting the cytoskeleton specifically and possibly resulting in fewer side effects. Here, we show that the preliminary use of screening in transgenic plants expressing subcellular markers can significantly reduce costs and focus the advanced characterization only on the most promising therapeutic molecules.
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