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微生物槐糖脂在体外抑制结直肠肿瘤细胞生长,并恢复 Apc 小鼠的血细胞比容。

Microbial sophorolipids inhibit colorectal tumour cell growth in vitro and restore haematocrit in Apc mice.

机构信息

School of Biomedical Sciences, Ulster University, Coleraine, BT52 1SA, UK.

Sorbonne Universités, UPMC Univ Paris 06, CNRS, Collège de France UMR 7574, Chimie de La Matière Condensée de Paris, UMR 7574, 75005, Paris, France.

出版信息

Appl Microbiol Biotechnol. 2022 Sep;106(18):6003-6016. doi: 10.1007/s00253-022-12115-6. Epub 2022 Aug 15.

Abstract

Sophorolipids are glycolipid biosurfactants consisting of a carbohydrate sophorose head with a fatty acid tail and exist in either an acidic or lactonic form. Sophorolipids are gaining interest as potential cancer chemotherapeutics due to their inhibitory effects on a range of tumour cell lines. Currently, most anti-cancer studies reporting the effects of sophorolipids have focused on lactonic preparations with the effects of acidic sophorolipids yet to be elucidated. We produced a 94% pure acidic sophorolipid preparation which proved to be non-toxic to normal human colonic and lung cells. In contrast, we observed a dose-dependent reduction in viability of colorectal cancer lines treated with the same preparation. Acidic sophorolipids induced apoptosis and necrosis, reduced migration, and inhibited colony formation in all cancer cell lines tested. Furthermore, oral administration of 50 mg kg acidic sophorolipids over 70 days to Apc mice was well tolerated and resulted in an increased haematocrit, as well as reducing splenic size and red pulp area. Oral feeding did not affect tumour numbers or sizes in this model. This is the first study to show that acidic sophorolipids dose-dependently and specifically reduces colon cancer cell viability in addition to reducing tumour-associated bleeding in the Apc mouse model. KEY POINTS: • Acidic sophorolipids are produced by yeast species such as Starmerella bombicola. • Acidic sophorolipids selectively killed colorectal cells with no effect on healthy gut epithelia. • Acidic sophorolipids reduced tumour-associated gut bleed in a colorectal mouse model.

摘要

槐糖脂是一种由碳水化合物槐糖组成的糖脂生物表面活性剂,带有脂肪酸尾巴,以酸性或内酯形式存在。槐糖脂因其对多种肿瘤细胞系的抑制作用而作为潜在的癌症化疗药物引起了人们的兴趣。目前,大多数报告槐糖脂作用的抗癌研究都集中在内酯型制剂上,而酸性槐糖脂的作用尚未阐明。我们制备了一种纯度为 94%的酸性槐糖脂制剂,证明其对正常人结肠和肺细胞无毒。相比之下,我们观察到用相同制剂处理的结直肠癌细胞系的活力呈剂量依赖性下降。酸性槐糖脂诱导细胞凋亡和坏死,减少迁移,并抑制所有测试的癌细胞系的集落形成。此外,在 Apc 小鼠中口服给予 50mg/kg 的酸性槐糖脂 70 天耐受性良好,导致红细胞压积增加,脾脏大小和红髓面积减少。口服喂养在该模型中对肿瘤数量或大小没有影响。这是第一项表明酸性槐糖脂除了减少 Apc 小鼠模型中的肿瘤相关出血外,还能剂量依赖性和特异性降低结肠癌细胞活力的研究。关键点:•酸性槐糖脂由 Starmerella bombicola 等酵母物种产生。•酸性槐糖脂选择性杀死结直肠细胞,对健康肠道上皮无影响。•酸性槐糖脂减少了结直肠小鼠模型中的肿瘤相关肠道出血。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb1a/9467956/6923ab0e93a1/253_2022_12115_Fig1_HTML.jpg

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