Vanadocene dichloride inhibits cell proliferation by targeting Aurora B

Abstract

Vanadocene dichloride (VDC) was shown to exhibit antitumor properties against a wide spectrum of tumor cell lines. Many studies have been carried out to reveal the bioactivities of VDC and the interaction mechanism of VDC with biological molecules in test tubes. One of the bioactivities of VDC is to arrest the cell cycle at the G2/M phase. However, its underlying mechanisms of action and cytotoxicity profile are still not fully understood. HeLa cells were used in this study, and the IC50 value of VDC was 8.61 μM after a 24-hour treatment. We used an immunofluorescence staining method to analyze the morphology of cells in the mitosis stage to elucidate what defects caused cell arrest in mitosis. Chromosomal misalignment was found to be the major phenotype. One of the proteins responsible for chromosome alignment at the metaphase is Aurora B kinase. Results of immunoblotting assay showed that Aurora B kinase activity was inhibited by VDC treatment. More than 50% of the Aurora B activity was inhibited when cells were treated with VDC at a concentration of 6.25 μM. That VDC was able to induce defects in chromosomal alignment at the metaphase by inhibiting the activity of Aurora B kinase is an important mechanism of VDC to be developed as an antitumor agent.

From Synthetic Simplified Marine Metabolite Analogues to New Selective Allosteric Inhibitor of Aurora B Kinase

“…We noted that typical chromosome alignment and spindle defects were observed as previously reported in Aurora B depletion or inhibition experiments. 70 Quantification of the H3S10ph signal versus the DAPI signal is represented in Figure 6B. The strongest reduction in the H3S10ph signal was obtained with compound CJ2-150 at 10 μM, similar to that obtained with ZM447439 at 1 μM.…”

“…Compared to the control, the H3S10ph signal was greatly reduced for both our compound and ZM447439 (Figure A). We noted that typical chromosome alignment and spindle defects were observed as previously reported in Aurora B depletion or inhibition experiments . Quantification of the H3S10ph signal versus the DAPI signal is represented in Figure B.…”

Vanadocene-functionalized mesoporous silica nanoparticles: platforms for the development of theranostic materials against breast cancer

“…Interestingly, based on the IC 50 values in relation to vanadium concentration for the metallodrug candidates (S1-S4), it appears that a modest loading of vanadium, approximately 0.4%-1.0% into the cell lines, was sufficient to induce cytotoxicity (figure 8). In contrast, previous studies with vanadocene dichloride and cisplatin have required metal concentrations of up to 30%-65% [35][36][37]. Therefore, it can be inferred that the metallodrugfunctionalized nanostructured systems in this study enhance the delivery of the active vanadium species into the cell lines.…”

In Vitro and In Vivo Biological Activities of Dipicolinate Oxovanadium(IV) Complexes

“…Vanadium compounds have been widely investigated due to a broad application in catalysis − and a wide range of pharmacological properties. − In the area of medicinal applications, the exploration of vanadium-based compounds has been focused on their insulin-mimetic properties, − ,− anticancer activities, − ,− antibacterial action, ,,,− and effects on enzymes. ,,, In particular, bis­(ethylmaltolato)­oxidovanadium­(IV) (BEOV) entered the phase IIa clinical trials as an antidiabetic agent and its improved pharmacokinetics relative to vanadyl sulfate was evidenced. − Vanadocene dichloride, (η 5 -C 5 H 5 ) 2 VCl 2 (C 5 H 5 = cyclopentadienyl), was demonstrated to have antitumor effects on a wide spectrum of cancer cells, including testicular cancer, leukemia, breast cancer, glioblastoma, and colon cancer. − ,− Among oxidovanadium­(IV) derivatives, special attention has been devoted to bis­(4,7-dimethyl-1,10-phenanthroline)-sulfatooxidovanadium­(IV) (Metvan), which was found to induce apoptosis in leukemia, multiple myeloma, and solid tumors such as breast, prostate, testis, and glio...…”