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

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-s...

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Bibliographic Details
Published in:Oncotarget 2015-04, Vol.6 (11), p.9295-9312
Main Authors: Xiang, Liping, Chi, Ting, Tang, Qiao, Yang, Xiang, Ou, Minrui, Chen, Xiufen, Yu, Xiaobo, Chen, Jianzhong, Ho, Rodney J Y, Shao, Jingwei, Jia, Lee
Format: Article
Language:English
Subjects:
Animals
Biological Products - pharmacology
Cell Adhesion - drug effects
Cell Adhesion - genetics
Cells, Cultured
Hep G2 Cells
HT29 Cells
Human Umbilical Vein Endothelial Cells
Humans
MCF-7 Cells
Mice
Mice, Inbred C57BL
Molecular Targeted Therapy
Neoplasm Metastasis
Neoplasms - pathology
Neoplasms - prevention & control
Pentacyclic Triterpenes - pharmacology
Prodrugs - pharmacology
Research Paper
Signal Transduction - drug effects
Signal Transduction - genetics
Triterpenes - pharmacology
Ursolic Acid
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Summary: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.
ISSN:1949-2553
1949-2553
DOI:10.18632/oncotarget.3261