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过度硫酸化对. 中提取的褐藻糖胶的组成、结构和体外抗肺癌活性的影响

Effect of Oversulfation on the Composition, Structure, and In Vitro Anti-Lung Cancer Activity of Fucoidans Extracted from .

机构信息

Faculty of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.

Center for Cancer Research, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.

出版信息

Mar Drugs. 2021 Apr 12;19(4):215. doi: 10.3390/md19040215.

DOI:10.3390/md19040215
PMID:33921340
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8069878/
Abstract

Intensive efforts have been undertaken in the fields of prevention, diagnosis, and therapy of lung cancer. Fucoidans exhibit a wide range of biological activities, which are dependent on the degree of sulfation, sulfation pattern, glycosidic branches, and molecular weight of fucoidan. The determination of oversulfation of fucoidan and its effect on anti-lung cancer activity and related signaling cascades is challenging. In this investigation, we used a previously developed fucoidan (SCA), which served as a native fucoidan, to generate two oversulfated fucoidan derivatives (SCA-S1 and SCA-S2). SCA, SCA-S1, and SCA-S2 showed differences in compositions and had the characteristic structural features of fucoidan by Fourier transform infrared (FTIR) and nuclear magnetic resonance (NMR) analyses. The anticancer properties of SCA, SCA-S1, and SCA-S2 against human lung carcinoma A-549 cells were analyzed in terms of cytotoxicity, cell cycle, Bcl-2 expression, mitochondrial membrane potential (MMP), expression of caspase-3, cytochrome release, Annexin V/propidium iodide (PI) staining, DNA fragmentation, and the underlying signaling cascades. Our findings indicate that the oversulfation of fucoidan promotes apoptosis of lung cancer cells and the mechanism may involve the Akt/mTOR/S6 pathway. Further in vivo research is needed to establish the precise mechanism whereby oversulfated fucoidan mitigates the progression of lung cancer.

摘要

在肺癌的预防、诊断和治疗领域已经进行了大量的努力。褐藻糖胶表现出广泛的生物活性，这些活性依赖于褐藻糖胶的硫酸化程度、硫酸化模式、糖苷支链和分子量。褐藻糖胶的过度硫酸化的测定及其对抗肺癌活性和相关信号级联的影响具有挑战性。在这项研究中，我们使用了一种先前开发的褐藻糖胶（SCA），作为天然褐藻糖胶，生成了两种过度硫酸化的褐藻糖胶衍生物（SCA-S1 和 SCA-S2）。SCA、SCA-S1 和 SCA-S2 的组成存在差异，并通过傅里叶变换红外（FTIR）和核磁共振（NMR）分析具有褐藻糖胶的特征结构特征。通过细胞毒性、细胞周期、Bcl-2 表达、线粒体膜电位（MMP）、caspase-3 表达、细胞色素 c 释放、Annexin V/碘化丙啶（PI）染色、DNA 片段化和潜在的信号级联分析，研究了 SCA、SCA-S1 和 SCA-S2 对人肺癌 A-549 细胞的抗癌特性。我们的研究结果表明，褐藻糖胶的过度硫酸化促进了肺癌细胞的凋亡，其机制可能涉及 Akt/mTOR/S6 途径。需要进一步的体内研究来确定过度硫酸化褐藻糖胶减轻肺癌进展的确切机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d39/8069878/bd469f3a7e16/marinedrugs-19-00215-g011.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d39/8069878/4e616f016c61/marinedrugs-19-00215-g005.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d39/8069878/bfab069ca076/marinedrugs-19-00215-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d39/8069878/37b3f13f612b/marinedrugs-19-00215-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d39/8069878/ab687743020a/marinedrugs-19-00215-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d39/8069878/f6feb683213e/marinedrugs-19-00215-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d39/8069878/bd469f3a7e16/marinedrugs-19-00215-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d39/8069878/b1b3a93073f6/marinedrugs-19-00215-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d39/8069878/5f0cb8915e15/marinedrugs-19-00215-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d39/8069878/35ed18a10075/marinedrugs-19-00215-g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d39/8069878/4e616f016c61/marinedrugs-19-00215-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d39/8069878/9a8ddee66bc5/marinedrugs-19-00215-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d39/8069878/bfab069ca076/marinedrugs-19-00215-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d39/8069878/37b3f13f612b/marinedrugs-19-00215-g008.jpg
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