RY10-4 suppressed metastasis of MDA-MB-231 by stabilizing ECM and E-cadherin.

Abstract

In the article, we investigated the anti-metastasis mechanism of RY10-4, an anti-tumor compound derived from protoapigenone, in breast tumor cells MB-MDA-231. The analog of protoapigenone with an unaromatic B-ring was verified to suppress the proliferation of several tumor cells by previous research that also showed that several tumor progression such as inducing apoptosis and anti-angiogenesis could be acted on by RY10-4. In the article, we investigated the mechanism about how RY10-4 suppressed the invasion of MDA-MB-231. Firstly, the transwells assays with and without matrigel were adapted to evaluate the anti-metastasis and anti-invasion activity. Much research had demonstrated that the ECM and E-cadherin/β-catenin complex play an important role in cell adhesion and the formation of the cell skeleton, and as we knew the abnormal and absent expression of ECM and E-cadherin/β-catenin complex are found in many malignant cells. The result demonstrated that the amount and distribution of E-cadherin/β-catenin complex were backed on track by RY10-4, and the expression of MMP-2/9 in MDA-MB-231, which functions as a major negative factor of ECM, was down-regulated after co-cultured with RY10-4. Furthermore the pathway related to MMP-2/9 and E-cadherin was assessed by the western blot. As the results showed, the MAPK pathway and the spread of β-catenin were affected by RY10-4 to exert the anti-metastasis on MDA-MB-231. Collectively, the research revealed a novel anti-tumor ability of RY10-4 by inhibiting migration and invasion in MDA-MB-231.

• Authors: Ziwei Liu, Zhimei Liu, Xiulan Zhang, Pingping Xue, Heng Zhang
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 68 Issue 4 Pg. 439-45 (May 2014) ISSN: 1950-6007 [Electronic] France
• PMID: 24721328 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Chemical References

• 2-(1-hydroxy-4-oxocyclohexa-2,5-dienyl)pyran-4-one
• Antineoplastic Agents
• Cadherins
• Pyrones
• beta Catenin

Topics

• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Blotting, Western
• Breast Neoplasms (drug therapy, pathology)
• Cadherins (metabolism)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Down-Regulation (drug effects)
• Extracellular Matrix (drug effects, metabolism)
• Female
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Neoplasm Invasiveness (prevention & control)
• Neoplasm Metastasis (prevention & control)
• Pyrones (pharmacology)
• beta Catenin (metabolism)