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一种五环三萜类天然产物——熊果酸及其前药US597可抑制细胞黏附途径中的靶点并预防癌症转移。

A pentacyclic triterpene natural product, ursolic acid and its prodrug US597 inhibit targets within cell adhesion pathway and prevent cancer metastasis.

作者信息

Xiang Liping, Chi Ting, Tang Qiao, Yang Xiang, Ou Minrui, Chen Xiufen, Yu Xiaobo, Chen Jianzhong, Ho Rodney J Y, Shao Jingwei, Jia Lee

机构信息

Cancer Metastasis Alert and Prevention Center and Pharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou 350002, China.

School of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350108, China.

出版信息

Oncotarget. 2015 Apr 20;6(11):9295-312. doi: 10.18632/oncotarget.3261.

DOI:10.18632/oncotarget.3261
PMID:25823660
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4496218/
Abstract

Here we showed that ursolic acid (UA), a pentacyclic triterpene natural product, and its novel prodrug derivative US597 suppressed cancer cells adhesion, invasion and migration. This effect was accompanied by inhibition of focal adhesion signaling pathway including alterations in ICAM-1, VCAM-1, E-selectin, P-selectin, integrin α6β1, FAK, Src, paxillin and PTEN. While oral administration of UA or US597 increases survival rate of melanoma lung metastasis in C57BL/6 mice, US597 treatment extend the survival rate above that of UA. Immunohistochemical analysis revealed that US597 treatment regulates ICAM-1, a biomarker of metastasis. We did not detect side effects with US597 in mice such as weight loss, viscera tissues toxicity and blood cell abnormalities. Thus, UA and US597 are potential drug candidates for preventing cancer metastasis. Molecular and cellular study data suggest that UA and US597 modulate expression of cell adhesion molecules within focal adhesion signaling pathway leading to cancer cell motility.

摘要

我们在此表明，熊果酸（UA），一种五环三萜天然产物，及其新型前药衍生物US597可抑制癌细胞的黏附、侵袭和迁移。这种效应伴随着对黏着斑信号通路的抑制，包括细胞间黏附分子-1（ICAM-1）、血管细胞黏附分子-1（VCAM-1）、E-选择素、P-选择素、整合素α6β1、黏着斑激酶（FAK）、Src、桩蛋白和磷酸酶及张力蛋白同源物（PTEN）的改变。口服UA或US597可提高C57BL/6小鼠黑色素瘤肺转移的存活率，而US597治疗可使存活率高于UA。免疫组织化学分析显示，US597治疗可调节转移生物标志物ICAM-1。我们在小鼠中未检测到US597的副作用，如体重减轻、内脏组织毒性和血细胞异常。因此，UA和US597是预防癌症转移的潜在候选药物。分子和细胞研究数据表明，UA和US597可调节黏着斑信号通路中细胞黏附分子的表达，从而导致癌细胞的运动。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c69a/4496218/f35539465c64/oncotarget-06-9295-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c69a/4496218/97901e0565b3/oncotarget-06-9295-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c69a/4496218/639a681e03db/oncotarget-06-9295-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c69a/4496218/05a15fd93874/oncotarget-06-9295-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c69a/4496218/5df83b8d6d76/oncotarget-06-9295-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c69a/4496218/bdec5fd3e028/oncotarget-06-9295-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c69a/4496218/3720c1449c0b/oncotarget-06-9295-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c69a/4496218/9e6ca9211e00/oncotarget-06-9295-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c69a/4496218/5f8e1c460531/oncotarget-06-9295-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c69a/4496218/f35539465c64/oncotarget-06-9295-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c69a/4496218/97901e0565b3/oncotarget-06-9295-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c69a/4496218/639a681e03db/oncotarget-06-9295-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c69a/4496218/05a15fd93874/oncotarget-06-9295-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c69a/4496218/5df83b8d6d76/oncotarget-06-9295-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c69a/4496218/bdec5fd3e028/oncotarget-06-9295-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c69a/4496218/3720c1449c0b/oncotarget-06-9295-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c69a/4496218/9e6ca9211e00/oncotarget-06-9295-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c69a/4496218/5f8e1c460531/oncotarget-06-9295-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c69a/4496218/f35539465c64/oncotarget-06-9295-g009.jpg

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