Department of Biological and Environmental Sciences and Technologies (Di.S.Te.B.A.), University of Salento, Via Monteroni, 73100 Lecce, Italy.
Oncology Group IDISSC and Biomedical Technology Centre (CTB), Biotecnology-B.V. Departament ETSIAAB, Universidad Politécnica de Madrid, 28223 Madrid, Spain.
Int J Mol Sci. 2023 Oct 5;24(19):14920. doi: 10.3390/ijms241914920.
Numerous studies have reported the pharmacological effects exhibited by , () 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 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.
许多研究报告了 ()表现出的药理作用,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识别表现出最强抗增殖和抗癌作用的馏分的预筛选方法。具体来说,我们使用涉及转基因植物的筛选方法研究了各种提取物馏分对细胞骨架的影响。肿瘤本质上是异质的,细胞骨架的成分,特别是微管蛋白,被认为是抗肿瘤药物的一个战略目标。为了考虑异质性,我们使用了不同的结直肠癌细胞系,特别是一种无论性别都最常见的癌症。在转移性患者中,化疗的有效性受到严重副作用和耐药性发展的限制。因此需要额外的治疗和抗增殖分子。在我们的研究中,我们使用了具有胃肠道分化标志物表达的结肠样细胞系(如 HT-29 细胞系)和具有上皮-间充质转化和 TGFβ 特征的未分化细胞系(如 DLD-1、SW480 和 SW620 细胞系)。我们表明,所有三种 提取物馏分都具有抗增殖作用,但对转基因植物的预筛选预计甲醇馏分可能是最有前途的,它专门针对细胞骨架,可能导致较少的副作用。在这里,我们表明,在表达亚细胞标志物的转基因植物中进行初步筛选可以显著降低成本,并仅将高级表征集中在最有前途的治疗分子上。