RY10-4 suppressed metastasis of MDA-MB-231 by stabilizing ECM and E-cadherin.
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.
School of Chemical Engineering & Pharmacy, Wuhan Institute of Technology, Xiongchu Avenue, Wuhan, China.
Ziwei
Z
Liu
Humanwell Healthcare (group) Co. Ltd, Gaoxing Avenue, Wuhan, China.
Zhimei
Z
Liu
School of Chemical Engineering & Pharmacy, Wuhan Institute of Technology, Xiongchu Avenue, Wuhan, China.
Xiulan
X
Zhang
Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation of Hubei Province, College of Pharmacy, Huazhong University of Science and Technology, Wuhan, China.
Pingping
P
Xue
School of Chemical Engineering & Pharmacy, Wuhan Institute of Technology, Xiongchu Avenue, Wuhan, China. Electronic address: zhzpthm@163.com.
Heng
H
Zhang
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D009362:Neoplasm Metastasis / Q000517:prevention & control; D011753:Pyrones / Q000494:pharmacology*; D051176:beta Catenin / Q000378:metabolism
C574037:2-(1-hydroxy-4-oxocyclohexa-2,5-dienyl)pyran-4-one; D000970:Antineoplastic Agents; D015820:Cadherins; D011753:Pyrones; D051176:beta Catenin
E-cadherin; MAPK; MMP-2/9; Metastasis; RY10-4; β-catenin