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Studies on a promising anticancer molecule of marine origin. Results of an interdisciplinary study.

机译:对海洋有希望的抗癌分子的研究。跨学科研究的结果。

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Poly-APS, a mixture of two of 3-octylpyridinium polymers, including 29 and 99 monomeric units, extracted from the Mediterranean sponge, Haliclona (Reniera) sarai, was demonstrated to exert strong specific and non-toxic acetylcholinesterase inhibition in vitro. Since the first '80s, we found that some tumour types, and in particular lung rumours present overexpression of acetylcholinesterase activity. Acetylcholinesterase is an enzyme associated to the cholinergic signal system, but is also involved in cell-to-cell communication driving embryonic development and in the regulation of several cellular features, such as apoptosis and cell movements, and is present in some tumour cells and biopsies. Cytotoxicity tests on immortalized and primary cell lines derived from lung rumour (NSCLC) showed a poly-APS dose-dependent selective reduction of cell viability, statistically significant. The same cells, exposed to the poly-APS salts exhibited a loss in the mitochondrial potential, showed positive response to the annexin V assay, and to the T-terminal assay, that are specific markers of the apoptotic event. What makes the poly-APS salts promising as anticancer therapy adjuvant is that they, at the concentrations inducing apoptosis in tumour cells, do not affect the viability of lymphocytes isolated from healthy patients. Moreover, three-dimensional cell cultures (spheroids) of tumour cells, on exposure to poly-APS show a decrease in the membrane-linked oligosaccharides, that are responsible for the adhesivity of the metastatic cells. Moreover, no effects were demonstrated on healthy organs, such as heart, liver, kidney of mice treated by poly-APS, and in vivo tumours showed a mass and cellular density significantly reduced. In this promising frame, the need emerges for the isolation of synthetic homologs of poly-APS molecules, in order to start a study for the therapeutical application of the drug.
机译:聚APS是从地中海海绵Saliclona(Reniera)sarai提取的两种3-辛基吡啶鎓聚合物(包括29和99个单体单元)的混合物,在体外具有较强的特异性和无毒乙酰胆碱酯酶抑制作用。自上世纪80年代以来,我们发现某些肿瘤类型,尤其是肺谣传出了乙酰胆碱酯酶活性的过表达。乙酰胆碱酯酶是一种与胆碱能信号系统相关的酶,但也参与细胞间通讯,驱动胚胎发育,并调控多种细胞特征,例如凋亡和细胞运动,并且存在于某些肿瘤细胞和活检组织中。对源自肺肿瘤(NSCLC)的永生和原代细胞系的细胞毒性测试显示,poly-APS剂量依赖性选择性降低细胞活力,具有统计学意义。暴露于聚APS盐的相同细胞显示出线粒体潜力,对膜联蛋白V检测和T末端检测呈阳性反应,这是凋亡事件的特异性标志物。使聚APS盐有望作为抗癌治疗佐剂的原因是,它们在诱导肿瘤细胞凋亡的浓度下不影响从健康患者体内分离的淋巴细胞的活力。此外,肿瘤细胞的三维细胞培养物(球体)在暴露于聚APS后显示出膜连接的寡糖减少,这是导致转移细胞粘附的原因。而且,未证明对用聚-APS治疗的小鼠的健康器官如心脏,肝脏,肾脏有影响,并且体内肿瘤显示质量和细胞密度显着降低。在这个有希望的框架中,需要分离聚APS分子的合成同源物,以便开始研究该药物的治疗应用。

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