拟半乳甘露聚糖及其硫酸盐衍生物:结构和抗黑色素瘤作用。

IF 5.4 2区 化学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Odair Braz Júnior, Aline Miranda Cristal, Daniel de Lima Bellan, Gustavo Rodrigues Rossi, Stellee Marcela Petris Biscaia, Camila Laís Gonçalves Ribeiro, Jacqueline Gonçalves dos Santos, Anderson Fraga da Cruz, João Luiz Aldinucci Buzzo, Helyn Barddal, Thales R. Cipriani, Marcelo Dias-Baruffi, Edvaldo da Silva Trindade, Fernanda Fogagnoli Simas* and Carolina Camargo de Oliveira*, 
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引用次数: 0

摘要

黑色素瘤是最具侵袭性的皮肤癌,具有高转移潜力,晚期治疗选择有限。多糖是一种很有前景的抗肿瘤药物,因此,本研究对瓜尔胶水解半乳甘露聚糖(GGH)及其硫酸衍生物(ghs)的抗黑色素瘤和免疫刺激作用进行了研究。GGH与具有抗结直肠癌活性的半乳糖凝集素-1配体DAVANAT具有结构相似性,而ggs具有抗凝血特性,类似于用于癌症患者的肝素。在体外,100 μg/mL GGH或GGHS均能抑制黑色素瘤细胞的侵袭,增加粘附,减小菌落大小,同时GGHS还能抑制增殖。这两种化合物都能结合半乳糖凝集素-3和-1,但在小鼠中只有GGH抑制肿瘤进展。两种治疗都刺激了巨噬细胞的促炎反应,包括活性氧的产生和细胞因子的分泌。虽然没有观察到体外淋巴细胞增殖,但CD3+细胞在转移肺中增加。这些结果提示GGH和ghs作为免疫刺激剂,GGH作为潜在的黑色素瘤辅助治疗。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Davanat-Mimetic Galactomannan and Its Sulfated Derivative: Structure and Antitumor Effects against Melanoma

Melanoma is the most aggressive skin cancer, with a high metastatic potential and limited treatment options in advanced stages. Polysaccharides are promising antitumor agents, and therefore, this study investigated a galactomannan from guar gum hydrolysis (GGH) and its sulfated derivative (GGHS) for their antimelanoma and immunostimulatory effects. GGH shares structural similarity with DAVANAT, a galectin-1 ligand with anticolorectal cancer activity, while GGHS has anticoagulant properties, like heparin used in cancer patients. In vitro, 100 μg/mL GGH or GGHS inhibited melanoma cell invasion, increased adhesion, and reduced colony size, while GGHS also reduced proliferation. Both compounds bind galectin-3 and -1, but only GGH suppressed tumor progression in mice. Both treatments stimulated macrophage proinflammatory responses, including reactive oxygen species production and cytokine secretion. Although in vitro lymphocyte proliferation was not observed, CD3+ cells increased in the metastatic lungs. These results suggest GGH and GGHS as immunostimulatory agents, with GGH as potential melanoma adjuvant therapy.

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来源期刊
Biomacromolecules
Biomacromolecules 化学-高分子科学
CiteScore
10.60
自引率
4.80%
发文量
417
审稿时长
1.6 months
期刊介绍: Biomacromolecules is a leading forum for the dissemination of cutting-edge research at the interface of polymer science and biology. Submissions to Biomacromolecules should contain strong elements of innovation in terms of macromolecular design, synthesis and characterization, or in the application of polymer materials to biology and medicine. Topics covered by Biomacromolecules include, but are not exclusively limited to: sustainable polymers, polymers based on natural and renewable resources, degradable polymers, polymer conjugates, polymeric drugs, polymers in biocatalysis, biomacromolecular assembly, biomimetic polymers, polymer-biomineral hybrids, biomimetic-polymer processing, polymer recycling, bioactive polymer surfaces, original polymer design for biomedical applications such as immunotherapy, drug delivery, gene delivery, antimicrobial applications, diagnostic imaging and biosensing, polymers in tissue engineering and regenerative medicine, polymeric scaffolds and hydrogels for cell culture and delivery.
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