n/a
Article Publish Status: FREE
Abstract Title:

Inhibition of tumor invasion and metastasis by targeting TGF-β-Smad-MMP2 pathway with Asiatic acid and Naringenin.

Abstract Source:

Mol Ther Oncolytics. 2021 Mar 26 ;20:277-289. Epub 2021 Jan 20. PMID: 33614911

Abstract Author(s):

Guang-Yu Lian, Qing-Ming Wang, Thomas Shiu-Kwong Mak, Xiao-Ru Huang, Xue-Qing Yu, Hui-Yao Lan

Article Affiliation:

Guang-Yu Lian

Abstract:

Transforming growth factorβ (TGF-β) has been shown to promote tumor invasion and metastasis by activating the matrix metalloproteinases (MMPs); however, signaling mechanisms remain controversial and therapies targeting MMPs are still suboptimal. In the present study, we found that combined therapy with Asiatic acid (AA), aSmad7 agonist, and Naringenin (NG), a Smad3 inhibitor, effectively retrieved the balance between Smad3 and Smad7 signaling in the TGF-β-rich tumor microenvironment and thus significantly suppressed tumor invasion and metastasis in mouse models of melanoma and lung carcinoma. Mechanistically, we unraveled that Smad3 acted as a transcriptional activator of MMP2 and as a transcriptional suppressor of tissue inhibitors of metalloproteinase-2 (TIMP2) via binding to 5' UTR of MMP2 and 3' UTR of TIMP2, respectively. Treatment with NG inhibited Smad3-mediated MMP2 transcription while increasing TIMP, whereas treatment with AA enhanced Smad7 to suppress TGF-β/Smad3 signaling, as well as the activation of MMP2 by targeting the nuclear factor-κB (NF-κB)-membrane-type-1 MMP (MT1-MMP) axis. Therefore, the combination of AA and NG additively suppressed invasion and metastasis of melanoma and lungcarcinoma by targeting TGF-β/Smad-dependent MMP2 transcription, post-translational activation, and function.

Print Options


This website is for information purposes only. By providing the information contained herein we are not diagnosing, treating, curing, mitigating, or preventing any type of disease or medical condition. Before beginning any type of natural, integrative or conventional treatment regimen, it is advisable to seek the advice of a licensed healthcare professional.

© Copyright 2008-2024 GreenMedInfo.com, Journal Articles copyright of original owners, MeSH copyright NLM.