Arene ruthenium(ii) complex, a potent inhibitor against proliferation, migration and invasion of breast cancer cells, reduces stress fibers, focal adhesions and invadopodia
Autor: | Jiangtu He, Xiao-Hui Wu, Qiong Wu, Wenjie Mei, Zhao Zhang, Fenyong Sun |
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Rok vydání: | 2014 |
Předmět: |
Cell
Biophysics Antineoplastic Agents Breast Neoplasms Cell Growth Processes Biochemistry Metastasis Biomaterials Focal adhesion Cell Movement Cell Line Tumor Stress Fibers medicine PTEN Humans Protein kinase B Cytoskeleton Focal Adhesions biology Cell Cycle Metals and Alloys Cancer medicine.disease Cell biology medicine.anatomical_structure Microscopy Fluorescence Chemistry (miscellaneous) Cell culture Invadopodia biology.protein Ruthenium Compounds Cell Surface Extensions |
Zdroj: | Metallomics : integrated biometal science. 6(12) |
ISSN: | 1756-591X |
Popis: | 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. |
Databáze: | OpenAIRE |
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