Arene ruthenium(II) complex, a potent inhibitor against proliferation, migration and invasion of breast cancer cells, reduces stress fibers, focal adhesions and invadopodia

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期刊

Metallomics


标题

Arene ruthenium(II) complex, a potent  inhibitor against proliferation, migration and invasion of breast cancer cells,  reduces stress fibers, focal adhesions and invadopodia


作者

Qiong Wu, Jiangtu He, Wenjie Mei, Zhao  Zhang, Xiaohui Wu and Fenyong Sun


摘要

Effective chemotherapy drugs for cancer  that would inhibit tumor growth and suppress metastasis are currently lacking.  In this study, a series of arene ruthenium complexes, [(η6-arene)Ru(H2iip)Cl]Cl (arene = p-cymene, RAWQ03; CH3C6H5, RAWQ04; and  C6H6,RAWQ11), were synthesized and their inhibitory activity against tumor cells  were evaluated. The results showed that the complex RAWQ11 inhibited the growth  of MDA-MB-231 breast cancer cells by inducing S-phase arrest, which is closely  related to the inhibition of cell mitosis-mediated cell nucleus damage. Further  studies showed that RAWQ11 can inhibit the invasion and metastasis of MDA-MB-231  cells. The morphology of MDA-MB-231 cells changed, the number of focal adhesions  decreased, and the stress fibers de-polymerized upon dealing with the complex  RAWQ11. The FITC-gelatin assay confirmed that the formation of invadopodia in  MDA-MB-231 cells was significantly blocked by RAWQ11. Furthermore, RAWQ11 can  block the AKT signal pathway by upregulating the PTEN expression through binding  and downregulating miR-21. These results demonstrated that this type of arene  ruthenium(II) complex can block the invadopodia formation by regulating the  PTEN/AKT signal pathway mediated by miR-21 to inhibit the invasion and  metastasis of breast cancer cells. Therefore, this complex can be used as a  potential dual functional agent to inhibit the growth and metastasis of tumor  cells.


原文链接

http://pubs.rsc.org/en/content/articlelanding/2014/mt/c4mt00158c

2017年02月08日

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