Breast cancer (BCa) is the second leading cause of morbidity and mortality due to cancer in women. There are concerted efforts to identify effective agents for treating TNBC. Over the years, cisplatin and its analogues have been used as anti-cancer agents, but other non-platinum metal complexes (e.g., those with copper(II), ruthenium(II), ruthenium(III), vanadium(IV) metal centers, etc.) have been reported to be used in anti-cancer therapy. Interestingly, biomedically relevant cobalt-containing compounds have provided promising results for cancer treatment. In our contribution to the fight against cancer, a novel cobalt(III) complex, [Co(phen)2(MeATSC)](NO3)3.2.5H2O.C2H5OH 1 (where phen = 1,10-phenanthroline and MeATSC = 9-anthraldehyde-N(4)-methylthiosemicarbazone) was synthesized, characterized; then anti-cancer studies were carried out to ascertain its antitumor potential. Elemental analysis, FTIR spectroscopy, 1H, 13C, and 59Co NMR spectroscopy, and high resolution electrospray ionization mass spectroscopy were used to determine its structure. The interaction of the complex 1 with calf thymus DNA (CT DNA) was investigated by absorption and fluorescence spectroscopic methods. UV-visible spectroscopic studies revealed only a weak interaction with CT DNA (Kb = 1.89 × 104 M-1), topoisomerase inhibition assays and cleavage studies reflect that complex 1 is an efficient catalytic inhibitor of human topoisomerases I and IIα. Based upon the results obtained from the MTS assay on 4T1-luc metastatic mammary breast cancer cells (IC50 = 34.4 ± 5.2 µM when compared to IC50 = 13.75 ± 1.08 mM for the control, cisplatin), further investigations into the molecular events initiated by exposure to complex 1 were investigated. Studies have shown that complex 1 activated both the apoptotic and autophagic signalling pathways in addition to causing dissipation of the mitochondrial membrane potential (ΔΨm). Furthermore, activation of cysteine-aspartic proteases3 (caspase 3) in a time- and concentration-dependent manner coupled with the ΔΨm studies implicated the intrinsic apoptotic pathway as the major regulator of cell death.

Insight into the molecular mechanism of action of the anti-cancer properties of a novel cobalt(III) complex with a thiosemicarbazone ligand

2019 Spring National Meeting

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