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.