New perspectives of cobalt tris(bipyridine) system: anti-cancer effect and its collateral sensitivity towards multidrug-resistant (MDR) cancers

Abstract

Platinating compounds including cisplatin, carboplatin, and oxaliplatin are common chemotherapeutic agents, however, patients developed resistance to these clinical agents after initial therapeutic treatments. Therefore, different approaches have been applied to identify novel therapeutic agents, molecular mechanisms, and targets for overcoming drug resistance. In this study, we have identified a panel of cobalt complexes that were able to specifically induce collateral sensitivity in taxol-resistant and p53-deficient cancer cells. Consistently, our reported anti-cancer functions of cobalt complexes 1–6 towards multidrug-resistant cancers have suggested the protective and non-toxic properties of cobalt metal-ions based compounds in anti-cancer therapies. As demonstrated in xenograft mouse model, our results also confirmed the identified cobalt complex 2 was able to suppress tumor growth in vivo. The anti-cancer effect of the cobalt complex 2 was further demonstrated to be exerted via the induction of autophagy, cell cycle arrest, and inhibition of cell invasion and P-glycoprotein (P-gp) activity. These data have provided alternative metal ion compounds for targeting drug resistance cancers in chemotherapies.

Co-SLD suppressed the growth of oral squamous cell carcinoma via disrupting mitochondrial function

“…Syntheses and properties of Co-SLD As shown in Figure 1(A), Co-SLD was prepared through the addition reaction of Co 2 (CO) 8 and intermediate which was synthesized by the reaction of between organic acids with sulindac and propargyl alcohol. Co-SLD was characterized by NMR, ESI-MS and IR spectroscopy.…”

“…Of note, platinum-based therapy such as platinum in combination with 5-fluorouracil and cetuximab is currently given as first-line regimen for recurrent and/or metastatic head and neck cancer [5,6]. But platinumbased regimens have a dismal prognosis and increase toxicity [7,8]. Furthermore, tumours often relapse with drug resistance and eventually promoted metastatic potential [9,10].…”

“…Currently, the development of metal complexes with nonplatinum central atoms including ruthenium [11], gold [12], silver [13], copper [14], zinc [15], Manganese [16], nickel [17], iridium [18] and cobalt [19] has been one of the hottest emerging areas of anticancer drug research. Among these, carbonyl cobalt complex has strong properties of cancer prevention including tumour growth/metastasis suppression [20], antiproliferative [21], DNA cleavage [22], apoptotic induction [23] and autophagy [8], which was more active than cisplatin on the human breast tumour cell lines (MCF-7 and MDA-MB-231) [24,25] and ovarian cancer cells (SKOV3/ DDP) [26]. With the concept of carbonyl metal CO-releasing molecules (CORMs) appearing, the anti-inflammatory effects were found through liberating CO to inhibit nitrite content [27].…”

Outlook on the Application of Metal-Liganded Bioactives for Stimuli-Responsive Release

“…Bioactive release usually ensues after ligand exchange by other nucleophiles in the biological milieu occurs. Moreover, both +2 and +3 cobalt species have been reported to possess no significant cell toxicity [ 41 , 42 ] at known doses. Pioneering work by Failes and co-workers therefore demonstrated that cobalt complexation to available “O” donor sites on metalloproteinase (MMP) inhibitors could result in two-fold design benefits [ 43 ].…”

Conjugates of Gold Nanoparticles and Antitumor Gold(III) Complexes as a Tool for Their AFM and SERS Detection in Biological Tissue

“…Among the large number of gold(III) complexes synthesized so far with the goal to overcome the toxic side effects of platinum(II) drugs in anticancer treatment [1,2], the compounds having aromatic N-containing heterocycles as ligands have gained special interest, as such ligands greatly increase the stability of these metal compounds under physiological conditions [3][4][5][6]. Moreover, N-containing heterocycles and their derivatives as the structural moieties of metal-based drugs confer to the metal center diverse biological activities, such as antitumor, antimicrobial, and anti-inflammatory [4,7]. For this reason, their tracking in biological tissues is of great importance [8,9].…”