Journal
CARBOHYDRATE POLYMERS
Volume 210, Issue -, Pages 225-233Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.carbpol.2019.01.024
Keywords
PSS; Structure-activity relationship; P-selectin; L-selectin; Lung metastasis
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Funding
- National Natural Science Fund [31701221]
- Shandong Science and Technology Development Planning Project [2014GGH215001]
- Qingdao Independent Innovation Project [15-4-13-zdzx-hy]
- Natural Science Foundation of Jiangsu Province [BK20170312]
- Qingdao Leading Talents Program [16-8-3-11-zhc]
- Qingdao National Laboratory for Marine Science and Technology [2017ASTCP-OS11]
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Selectins dominate the formation of the metastasis niche and are considered important targets for exploring antimetastatic drugs. In this study, we evaluated the effect of the marine drug propylene glycol alginate sodium sulfate (PSS) and a series of PSS derivatives on P-, L- or E-selectin-mediated binding with tumor cells. We found that PSS effectively prevented the binding of P- or L-selectin with tumor cells. Moreover, the structure-activity relationship study indicated that the activity of PSS is related to the sulfate group at the C-2/C-3 position, the propylene glycol substituent at the C-6 position, the ratio of guluronic acid to mannuronic acid, and the molecular weight. Additionally, PSS derivatives significantly suppressed lung metastasis in vivo. Our results demonstrated that PSS and its derivatives are potential antimetastatic drugs candidates.
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