二异源葡糖胺共轭物提高了癌细胞株的促凋亡活性和选择性活性。

IF 2.4 4区 生物学 Q4 CELL BIOLOGY
Martínez Mata Sergio Iván, Escobar Sánchez María Luisa, López Muñoz Hugo, Hilario Martínez Jazmín Ciciolil, Sandoval Ramírez Jesús, Aparicio Sánchez Uriel Yair, Sánchez Sánchez Luis
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引用次数: 0

摘要

背景信息:植物类固醇 diosgenin((25R)-螺甾-5-烯-3β-醇;1)具有抗增殖和细胞凋亡活性。众所周知,将葡萄糖与与薯蓣皂苷相连的两个鼠李糖(查考三糖苷框架)结合在一起可增加其凋亡活性。然而,有关薯蓣皂苷葡萄糖胺苷对不同癌细胞类型和细胞死亡的影响尚未完全探明:本研究报告了薯蓣皂苷及其糖基化衍生物((25R)-螺甾-5-烯-3β-基 β-D-吡喃葡萄糖苷;2)的抗增殖、细胞毒性和细胞凋亡活性。本研究还探讨了两种薯蓣皂苷氨基葡萄糖衍生物,即薯蓣皂苷 2-乙酰氨基-2-脱氧-β-D-吡喃葡萄糖苷(3)和薯蓣皂苷 2-氨基-2-脱氧-β-D-吡喃葡萄糖苷盐酸盐(4)对不同癌细胞株的影响。我们发现,所有化合物都能影响细胞的增殖活性,且毒性极低。此外,所有癌细胞株都表现出与凋亡过程相应的形态和生化特征。与使用薯蓣皂苷处理的细胞株相比,使用化合物 2、3 和 4 处理的细胞株凋亡率更高。此外,化合物 3 和 4 比化合物 1 和 2 更能诱导细胞凋亡。这些结果表明,将氨基葡萄糖与附着于二缩二烯醇的改性氨基葡萄糖相结合,比二缩二烯醇或其糖基化衍生物(化合物 2)具有更强的凋亡效应。此外,薯蓣皂苷和上述苷类对肿瘤细胞具有选择性作用,因为人类淋巴细胞、角质细胞(HaCaT)和上皮细胞(CCD841)的增殖能力没有受到明显影响:总之,这些结果表明,双歧因子氨基葡萄糖化合物对癌细胞株具有抗增殖作用,并且比单独使用双歧因子更有效地诱导细胞凋亡,而不影响非肿瘤细胞:这项研究证明了双歧氨基葡萄糖化合物对癌细胞株的促凋亡和选择性活性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Diosgenyl glucosamine conjugates increase pro-apoptotic and selective activities in cancer cell lines

Diosgenyl glucosamine conjugates increase pro-apoptotic and selective activities in cancer cell lines

Diosgenyl glucosamine conjugates increase pro-apoptotic and selective activities in cancer cell lines

Background Information

Antiproliferative and apoptotic activities have been attributed to the phytosteroid diosgenin ((25R)-spirost-5-en-3β-ol; 1). It is known that combining glucose with two rhamnoses (the chacotrioside framework) linked to diosgenin increases its apoptotic activity. However, the effects of diosgenin glucosamine glycosides on different cancer cell types and cell death have not been entirely explored.

Results

This study reports the antiproliferative, cytotoxic, and apoptotic activities of diosgenin and its glycosylated derivative ((25R)-spirost-5-en-3β-yl β-D-glucopyranoside; 2). It also explores the effects of two diosgenin glucosamine derivates, diosgenin 2-acetamido-2-deoxy-β-D-glucopyranoside (3), and diosgenin 2-amino-2-deoxy-β-D-glucopyranoside hydrochloride (4), on different cancer cell lines. We found that all the compounds affected proliferative activity with minimal toxicity. In addition, all cancer cell lines showed morphological and biochemical characteristics corresponding to an apoptotic process. Apoptotic cell death was higher in all cell lines treated with compounds 2, 3 and 4 than in those treated with diosgenin. Moreover, compounds 3 and 4 induced apoptosis better than compounds 1 and 2. These results suggest that combining glucosamine with modified glucosamine attached to diosgenin has a greater apoptotic effect than diosgenin or its glycosylated derivative (compound 2). Furthermore, diosgenin and the abovementioned glycosides had a selective effect on tumour cells since the proliferative capacity of human lymphocytes, keratinocytes (HaCaT) and epithelial cells (CCD841) was not significantly affected.

Conclusions

Altogether, these results demonstrate that diosgenin glucosamine compounds exert an antiproliferative effect on cancer cell lines and induce apoptotic effects more efficiently than diosgenin alone without affecting non-tumour cells.

Significance

This study evidences the pro-apoptotic and selective activities of diosgenyl glucosamine compounds in cancer cell lines.

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来源期刊
Biology of the Cell
Biology of the Cell 生物-细胞生物学
CiteScore
5.30
自引率
0.00%
发文量
53
审稿时长
>12 weeks
期刊介绍: The journal publishes original research articles and reviews on all aspects of cellular, molecular and structural biology, developmental biology, cell physiology and evolution. It will publish articles or reviews contributing to the understanding of the elementary biochemical and biophysical principles of live matter organization from the molecular, cellular and tissues scales and organisms. This includes contributions directed towards understanding biochemical and biophysical mechanisms, structure-function relationships with respect to basic cell and tissue functions, development, development/evolution relationship, morphogenesis, stem cell biology, cell biology of disease, plant cell biology, as well as contributions directed toward understanding integrated processes at the organelles, cell and tissue levels. Contributions using approaches such as high resolution imaging, live imaging, quantitative cell biology and integrated biology; as well as those using innovative genetic and epigenetic technologies, ex-vivo tissue engineering, cellular, tissue and integrated functional analysis, and quantitative biology and modeling to demonstrate original biological principles are encouraged.
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