A series of bis-salicylaldimine
ligands bearing two ON-donor functions were reacted with
dichloro(p-cymene)ruthenium(II) dimer in the presence of base (NaOAc) and a series of four dimetallic Ru(II) arene complexes (Ru(p-cymene))2(bis-salicylaldimine)Cl2 (C1C4) were prepared. These complexes were obtained in excellent isolated yields and characterized in detail by using different spectroscopic techniques. The structure of C1 was also determined in solid state by single crystal X-ray analysis. These complexes were studied for their cytotoxic effect against three different types of human
cancer cells including
hepatocellular carcinoma (HepG2),
non-small-cell lung cancer (A549) and
breast cancer (MCF-7) cells by MTT assay. These complexes showed considerable cytotoxic effect in all the above-mentioned cell lines that was comparable to the effect of
cisplatin. C1 and C2 showed moderate anticancer effect while C3 and C4 showed reasonable cytotoxicity. We found the cytotoxicity was increased in series from C1 to C4 representing the effect of
ligand modification from small to bulky group at the
amine functionality of the salicylaldimine. We selected C3 and C4 for mechanistic anticancer study in MCF-7 cells. The
acridine orange/
ethidium bromide and
DAPI staining assays of MCF-7 cells treated with Ru(II) complexes showed apoptosis in
cancer cells. Similarly, these complexes induced p53
protein expression in MCF-7 cells. Further, increased
mRNA levels of p63, p73, PUMA, BAX and NOXA genes were observed in response to the treatment with C3 and C4, while cyclinD1, MMP3 and ID1 gene expression was significantly reduced. We found reduced invasion ability in
breast cancer cells treated with C3 and C4. Taken together, we demonstrated that bis-salicylaldimine based dimetallic Ru-(
p-cymene) complexes exerts anticancer effects by p53 pathway, suggesting the promising chemotherapeutic potentials of these Ru(II) complexes for the treatment of
cancer. This study may further pave for their in depth in vitro or in vivo anticancer investigations.