Ru(ii)-Naphthoquinone complexes with high selectivity for triple-negative breast cancer

Abstract

Ru(ii)/lapachol complex shows significant selectivity for triple negative breast cancer (TNBC) compared to the non-tumor human breast epithelial cell line.

A Novel Ruthenium(II) Complex With Lapachol Induces G2/M Phase Arrest Through Aurora-B Kinase Down-Regulation and ROS-Mediated Apoptosis in Human Prostate Adenocarcinoma Cells

“…Recognized studies also demonstrated that lapachol can generate semiquinone radicals by bioreduction in intracellular hypoxic conditions, which is involved with the production of reactive oxygen species (ROS) selectively in cancer cells ( 13 , 14 ). Later, the anticancer potential of lapachol and its analogs have been extensively explored ( 15 , 16 ). These studies reported the ability of lapachol to induce mitochondria-mediated cellular apoptosis by activating caspases and PARP ( 17 ).…”

Exploring the Potential of Metallodrugs as Chemotherapeutics for Triple Negative Breast Cancer

“…[99,103] Correa and co-workers have also explored the coordination of lapachol to Ru derivatives (like compound 39 [Ru-(Lap)(dppe)(bipy)]PF 6 , Scheme 6). [110] Exposure of MDA-MB-231 cells to compound 39 showed a high cytotoxic effect (IC 50 = 0.15 � 0.01 μM, 48 h ) as well as an apoptotic mechanism of cell death with an increase of sub-G1 cell cycle arrest occurring with treatment. A loss of ΔΨm was observed, suggesting an interaction with the mitochondrial membrane potential and indicative of early apoptosis.…”

“…The activity of coordination cationic compounds (most relevant depicted in Scheme 5) in TNBC are linked to a variety of cellular mechanisms such as DNA interactions and apoptotic cell death, among others. [93][94][95][96][97][98][99][100][101][102][103][104][105][106][107][108][109][110][111][112] Ratanaphan and co-workers focused on elucidating cellular effects on BRCA1-defective cells with compound 32 ([Ru(Clazpy) 2 phen]Cl 2 • 8H 2 O in Scheme 5), a Ru(II) coordinated complex with the bidentate ligand 5-chloro-2-(phenylazo)pyridine. [94] Cytotoxicity was observed in MDA-MB-231 (IC 50 = 13.2 � 0.3 μM, 24 h) and BRCA1-defective HCC-1937 (IC 50 = 1.8 � 0.1 μM, 24 h) cell lines, along with cell cycle inhibition at G2/M phase and an apoptotic mechanism of cell death.…”

“…All this evidence taken together suggests mitochondrial involvement in the mechanism of action for 39). [110] Cominetti and co-workers have also focused on coordination Ru(II) compounds containing bioactive ligands. [111][112][113] Compound 40 [Ru(GA)(dppe) 2 ]PF 6 (Ru(GA) in Scheme 6) is a ruthenium(II) biphosphane complex containing a gallic acid ligand, which is a triphenol found in the plant kingdom that is active in a number of antitumor signaling pathways.…”

“…Ruthenium (II) coordination compounds containing biologically active ligands that have undergone preclinical TNBC studies. [99,103,110,111,113] was also determined that TfR receptors play a role in Ru(GA) transport into tumor cells. TfRs are overexpressed in cancer cells, and were silenced in cell line MDA-MB-231 through anti-TfR monoclonal antibodies s725 and s727 transfection.…”