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褐藻岩藻聚糖硫酸酯的结构及其在黑色素瘤和乳腺癌细胞集落形成模型中的代谢活性。

Structure and Metabolically Oriented Efficacy of Fucoidan from Brown Alga in the Model of Colony Formation of Melanoma and Breast Cancer Cells.

机构信息

G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch of the Russian Academy of Sciences, 159, prosp. 100 Let Vladivostoku, Vladivostok 690022, Russia.

Key Laboratory for Applied Microbiology of Shandong Province, Biology Institute of Shandong Academy of Sciences, Jinan 250014, China.

出版信息

Mar Drugs. 2023 Sep 10;21(9):486. doi: 10.3390/md21090486.

Abstract

This work reports the detailed structure of fucoidan from (2SmF2) and its ability to potentiate the inhibitory effect of glycolysis inhibitor 2-deoxy-d-glucose (2-DG). 2SmF2 was shown to be sulfated and acetylated galactofucan containing a main chain of alternating residues of 1,3- and 1,4-linked α-l-fucopyranose, fucose fragments with monotonous 1,3- and 1,4-type linkages (DP up to 3), α-d-Gal-(1→3)-α-L-Fuc disaccharides, and 1,3,4- and 1,2,4-linked fucose branching points. The sulfate groups were found at positions 2 and 4 of fucose and galactose residues. 2SmF2 (up to 800 µg/mL) and 2-DG (up to 8 mM) were not cytotoxic against MDA-MB-231 and SK-MEL-28 as determined by MTS assay. In the soft agar-based model of cancer cell colony formation, fucoidan exhibited weak inhibitory activity at the concentration of 400 µg/mL. However, in combination with low non-cytotoxic concentrations of 2-DG (0.5 or 2 mM), 2SmF2 could effectively inhibit the colony formation of SK-MEL-28 and MDA-MB-231 cells and decreased the number of colonies by more than 50% compared to control at the concentration of 200 µg/mL. Our findings reveal the metabolically oriented effect of fucoidan in combination with a glycolysis inhibitor that may be beneficial for a therapy for aggressive cancers.

摘要

这项工作报道了褐藻糖胶(2SmF2)的详细结构及其增强糖酵解抑制剂 2-脱氧-D-葡萄糖(2-DG)抑制作用的能力。结果表明,2SmF2 是一种硫酸化和乙酰化的半乳岩藻聚糖,其主链由交替的 1,3-和 1,4-连接的α-L-岩藻糖吡喃糖残基、具有单调的 1,3-和 1,4-型键(DP 高达 3)的岩藻糖片段、α-d-Gal-(1→3)-α-L-Fuc 二糖以及 1,3,4-和 1,2,4-连接的岩藻糖分支点组成。硫酸基团位于岩藻糖和半乳糖残基的 2 位和 4 位。通过 MTS 测定,2SmF2(高达 800 µg/mL)和 2-DG(高达 8 mM)对 MDA-MB-231 和 SK-MEL-28 均无细胞毒性。在基于软琼脂的癌细胞集落形成模型中,褐藻糖胶在 400 µg/mL 的浓度下表现出较弱的抑制活性。然而,在与低非细胞毒性浓度的 2-DG(0.5 或 2 mM)联合使用时,2SmF2 可以有效抑制 SK-MEL-28 和 MDA-MB-231 细胞的集落形成,并在 200 µg/mL 浓度下使集落数量比对照减少 50%以上。我们的研究结果揭示了褐藻糖胶与糖酵解抑制剂联合使用的代谢定向作用,这可能对侵袭性癌症的治疗有益。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/539b/10532595/444228f83dd3/marinedrugs-21-00486-g001.jpg

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