title: Arene ruthenium(ii) complex, a potent inhibitor against proliferation, migration and invasion of breast cancer cells, reduces stress fibers, focal adhesions and invadopodia.
abstract: 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.
authors.affiliation: School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, P. R. China. wenjiemei@126.com.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Wu
authors.forename: Jiangtu
authors.initials: J
authors.lastname: He
authors.forename: Wenjie
authors.initials: W
authors.lastname: Mei
authors.forename: Zhao
authors.initials: Z
authors.lastname: Zhang
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Wu
authors.forename: Fenyong
authors.initials: F
authors.lastname: Sun
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D022081:Cell Surface Extensions / Q000187:drug effects*; D003599:Cytoskeleton / Q000187:drug effects; D022001:Focal Adhesions / Q000187:drug effects*; D006801:Humans; D008856:Microscopy, Fluorescence; D017975:Ruthenium Compounds / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D022502:Stress Fibers / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D017975:Ruthenium Compounds