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来自褐藻 Dictyota dichotoma 的昆布多糖及其硫酸化衍生物作为黑素瘤治疗中的辐射防护剂和辐射增敏剂。

Laminaran from brown alga Dictyota dichotoma and its sulfated derivative as radioprotectors and radiosensitizers in melanoma therapy.

机构信息

Laboratory of Enzyme Chemistry, G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-Eastern Branch, Russian Academy of Sciences, Vladivostok, Russian Federation.

出版信息

Carbohydr Polym. 2019 Feb 15;206:539-547. doi: 10.1016/j.carbpol.2018.11.008. Epub 2018 Nov 10.

DOI:10.1016/j.carbpol.2018.11.008
PMID:30553355
Abstract

The laminarans are neutral water-soluble β-D-glucans of brown algae possessing potent immunomodulating, radioprotective, and anticancer activities. The aim of the present study was to investigate in vitro anticancer, radioprotective, and radiosensitizing activities of laminaran from brown alga Dictyota dichotoma and its sulfated derivative. The native and sulfated laminarans by themselves at non-toxic doses possessed significant anticancer activity against melanoma cells. Both polysaccharides protected normal epidermal cells, while only sulfated laminaran was able to sensitize melanoma cells to X-rays irradiation resulting in significant inhibition of cell proliferation, colony formation, and migration of cancer cells. The molecular mechanism of this action was related to the inhibition of MMP-2 and MMP-9 proteinases activity as well as down-regulation of kinases' phosphorylation of ERK1/2 signaling cascade. Taken together, the combination of sulfated derivative of laminaran from D. dichotoma with X-ray may serve as a potential treatment strategy for human melanoma.

摘要

裂褶菌是一种具有免疫调节、放射保护和抗癌活性的中性水溶性β-D-葡聚糖。本研究旨在研究来自褐藻 Dictyota dichotoma 的裂褶菌及其硫酸化衍生物的体外抗癌、放射保护和放射增敏活性。在非毒性剂量下,天然和硫酸化的裂褶菌本身具有显著的抗黑色素瘤细胞活性。两种多糖均能保护正常表皮细胞,而只有硫酸化的裂褶菌能够使黑色素瘤细胞对 X 射线照射敏感,从而显著抑制癌细胞的增殖、集落形成和迁移。这种作用的分子机制与抑制 MMP-2 和 MMP-9 蛋白酶活性以及下调 ERK1/2 信号级联激酶的磷酸化有关。总之,裂褶菌硫酸化衍生物与 X 射线的联合应用可能成为人类黑色素瘤的潜在治疗策略。

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