Anticancer activity and mechanism of bis-pyrimidine based dimetallic Ru(II)( η6-p-cymene) complex in human non-small cell lung cancer via p53-dependent pathway.

Anticancer activity and mechanism of bis-pyrimidine based dimetallic Ru(II)(η6-p-cymene) complex in human non-small cell lung cancer via p53-dependent pathway. J Inorg Biochem. 2019 Feb 23;194:52-64 Authors: Bhatti MZ, Ali A, Duong HQ, Chen J, Rahman FU Abstract Non-small cell lung cancer (NSCLC) is the most common cancer worldwide, which is related with poor prognosis and resistance to chemotherapy. Notably, ruthenium-based complexes have emerged as good alternative to the currently used platinum-based drugs for cancer therapy. In the present study, we synthesized a novel bis-pyrimidine based ligand 1,3-bis(2-methyl-6-(pyridin-2-yl)pyrimidin-4-yl)benzene (L) and used it in the synthesis of a dimetallic Ru(II) cymene complex [(Ru(η6-p-cymene)Cl)2(1,3-bis(2-methyl-6-(pyridin-2-yl)pyrimidin-4-yl)benzene)] (L-Ru). We checked the stability of this complex in solution state in D2O/DMSO‑d6 mixture and found it to be highly stable under these conditions. We determined the anticancer activity and mechanism of action of L-Ru in human NSCLC A549 and A427 by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and related biological analyses. These results revealed that L-Ru exerted a strong inhibitory effect on the cells proliferation,G0/G1-arrest, accompanied with upregulation of p53, p21, p15, cleaved Poly (ADP-ribose) polymerase (PARP) protein and downregulation of cell cycle markers. L-Ru inhibited cell migration and inva...
Source: Journal of Inorganic Biochemistry - Category: Biochemistry Authors: Tags: J Inorg Biochem Source Type: research