Vanadium(V) tris-3,5-di-tert-butylcatecholato complex: Links between speciation and anti-proliferative activity in human pancreatic cancer cells

Griffin, Edie; Levina, Aviva; Lay, Peter A.

doi:10.1016/j.jinorgbio.2019.110815

Cited by 28 publications

(48 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…80 The use of V(V/IV) and other metal complexes as anticancer drugs will likely require them to be sufficiently stable in the extracellular environment to enter the cells intact and to release the toxic metal ion and/or the ligands within the cell. 12,15,60,78,80−82 The increasing stability and lipophilicity of V(V/IV) complexes with organic ligands is also likely to affect their biological activity by changing the ratio of HSA vs Tf binding in the blood, 43,80 which will be the subject of future studies.…”

Section: ■ Discussionmentioning

confidence: 99%

“…These data are also consistent with real-time proliferation assays using another epithelial cancer cell line, PANC-1, which showed strong inhibition of cell proliferation by 10 μM V(V) in the absence of significant cell apoptosis or necrosis. 43 The presence of physiological concentrations of human apoTf (30 μM) with Fe(III)-NTA (15 μM) as an Fe(III) source 44 that produced partially Fe-saturated Tf (designated as Fe 0.5 Tf) 37 in the medium led to a drastic decrease in V antiproliferative activity (red lines in Figure 1; IC 50 = 50 ± 1 and 52 ± 6 μM V, Figure 2a). In contrast, fully Fe(III) saturated human Tf (Fe 2 Tf, 30 μM) did not cause significant changes in V antiproliferative activity in comparison with the experiments in the absence of added proteins (blue lines in Figure 1; IC 50 = 12.8 ± 0.2 and 15.8 ± 0.8 μM V in Figure 2a).…”

Section: Effect Of Serum Proteins On the Antiproliferativementioning

confidence: 99%

See 1 more Smart Citation

Vanadium(V/IV)–Transferrin Binding Disrupts the Transferrin Cycle and Reduces Vanadium Uptake and Antiproliferative Activity in Human Lung Cancer Cells

Levina

Lay

2020

Inorg. Chem.

Self Cite

View full text Add to dashboard Cite

The role of vanadium binding to transferrin (Tf) in the biological activities of vanadium-based drugs is a matter of considerable debate. In order to determine whether V(V) and/or V(IV) binding to Tf (in apo, monoferric(III), and diferric(III) forms) enhances or inhibits biological activities, cellular V uptake and in vitro antiproliferative activity were examined in the presence and absence of different forms of Tf and other biomolecules under normoxic conditions. These data were combined with studies on V–Tf binding in cell culture medium and its role in Tf interactions with transferrin receptor 1 (TfR1), using the biolayer interferometry (BLI) model of the Tf cycle that was developed in our group. The results showed that both V(V) and V(IV) oxidation states efficiently bind to vacant Fe(III) binding sites of Tf even in the presence of a 20-fold molar excess of albumin, although V does not displace Tf-bound Fe(III) under these conditions. Binding of V(V) or V(IV) to Tf in cell culture medium drastically reduced its cellular uptake and antiproliferative activity in the A549 (human lung cancer) cell line that expresses TfR1. BLI and gel electrophoresis studies showed that V(V/IV) binding to partially Fe(III) saturated Tf did not enhance the affinity of Tf binding to TfR1 at pH 7.4 but did disrupt Tf conformational changes under endosome-mimicking conditions (pH 5.6, 0.10 mM citrate). Hence, it is postulated that the absence of a significant cellular uptake of Tf-bound V(V/IV) is likely to be due to the return of undissociated V(V/IV)–Tf adducts to the cell surface after the endosomal step. Collectively, these data show that the biotransformation of V-based drugs leads to V(V/IV)–Tf binding in the blood serum and inhibits, rather than enhances, the biological activity of such drugs under aerobic conditions. These results indicate that the design of V-based drugs that are stable enough to survive in the blood, enter cells intact, and release the active components intracellularly is likely to be required for their clinical success.

show abstract

Section: ■ Discussionmentioning

confidence: 99%

Section: Effect Of Serum Proteins On the Antiproliferativementioning

confidence: 99%

Vanadium(V/IV)–Transferrin Binding Disrupts the Transferrin Cycle and Reduces Vanadium Uptake and Antiproliferative Activity in Human Lung Cancer Cells

Levina

Lay

2020

Inorg. Chem.

Self Cite

View full text Add to dashboard Cite

show abstract

“…51 V spectra were recorded using parameters reported previously [12,69] at 157.85 MHz. The chemical shifts were obtained using an external reference using 100 mM Na 3 VO 4 solution in 1.0 M NaOH ([VO 4 ] 3− signal at −541 ppm) [70]. The concentrations of each vanadate species V x were calculated from the fractions of the total integrated areas using the following equation: [V x ] = (A x /A t ) × ([V t ]/n), where A x corresponds to the area measured for the x vanadate species with n as the oligomer number (number of vanadium atoms), A t is the sum of the measured areas and [V t ] is the total vanadate concentration [71].…”

Section: Kinetic Studiesmentioning

confidence: 99%

Kinetic Studies of Sodium and Metforminium Decavanadates Decomposition and In Vitro Cytotoxicity and Insulin- Like Activity

et al. 2020

View full text Add to dashboard Cite

The kinetics of the decomposition of 0.5 and 1.0 mM sodium decavanadate (NaDeca) and metforminium decavanadate (MetfDeca) solutions were studied by 51V NMR in Dulbecco’s modified Eagle’s medium (DMEM) medium (pH 7.4) at 25 °C. The results showed that decomposition products are orthovanadate [H2VO4]− (V1) and metavanadate species like [H2V2O7]2− (V2), [V4O12]4− (V4) and [V5O15]5− (V5) for both compounds. The calculated half-life times of the decomposition reaction were 9 and 11 h for NaDeca and MetfDeca, respectively, at 1 mM concentration. The hydrolysis products that presented the highest rate constants were V1 and V4 for both compounds. Cytotoxic activity studies using non-tumorigenic HEK293 cell line and human liver cancer HEPG2 cells showed that decavanadates compounds exhibit selectivity action toward HEPG2 cells after 24 h. The effect of vanadium compounds (8–30 μM concentration) on the protein expression of AKT and AMPK were investigated in HEPG2 cell lines, showing that NaDeca and MetfDeca compounds exhibit a dose-dependence increase in phosphorylated AKT. Additionally, NaDeca at 30 µM concentration stimulated the glucose cell uptake moderately (62%) in 3T3-L1 adipocytes. Finally, an insulin release assay in βTC-6 cells (30 µM concentration) showed that sodium orthovanadate (MetV) and MetfDeca enhanced insulin release by 0.7 and 1-fold, respectively.

show abstract

“…In fact, there are several similarities in some metabolic pathways used by diabetes mellitus and cancer [ 26 , 27 , 28 , 29 , 30 , 31 , 32 ]. Vanadate and oligovanadates specifically act as anti-cancer drugs, as shown recently for studies with pancreatic cancer and malignant melanoma [ 33 , 34 , 35 ]. Additionally, the compound bis(4,7-dimethyl-1,10-phenanthroline) sulfatooxidovanadium(IV), known as Metvan, has been recently used in cytotoxicity studies with human osteosarcoma (MG-63) and human colorectal adenocarcinoma (HT-29) cell lines, displaying impaired cell viability of both cancer cell lines in a low concentration range (0.25–5.0 μM) [ 36 ].…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Crystal Structure, and Computational Methods of Vanadium and Copper Compounds as Potential Drugs for Cancer Treatment

et al. 2020

View full text Add to dashboard Cite

Transition metal-based compounds have shown promising uses as therapeutic agents. Among their unique characteristics, these compounds are suitable for interaction with specific biological targets, making them important potential drugs to treat various diseases. Copper compounds, of which Casiopeinas® are an excellent example, have shown promising results as alternatives to current cancer therapies, in part because of their intercalative properties with DNA. Vanadium compounds have been extensively studied for their pharmacological properties and application, mostly in diabetes, although recently, there is a growing interest in testing their activity as anti-cancer agents. In the present work, two compounds, [Cu(Metf)(bipy)Cl]Cl·2H2O and [Cu(Impy)(Gly)(H2O)]VO3, were obtained and characterized by visible and FTIR spectroscopies, single-crystal X-ray diffraction, and theoretical methods. The structural and electronic properties of the compounds were calculated through the density functional theory (DFT) using the Austin–Frisch–Petersson functional with dispersion APFD, and the 6-311 + G(2d,p) basis set. Non-covalent interactions were analyzed using Hirshfeld surface analysis (HSA) and atom in molecules analysis (AIM). Additionally, docking analysis to test DNA/RNA interactions with the Casiopeina-like complexes were carried out. The compounds provide metals that can interact with critical biological targets. In addition, they show interesting non-covalent interactions that are responsible for their supramolecular arrangements.

show abstract

Vanadium(V) tris-3,5-di-tert-butylcatecholato complex: Links between speciation and anti-proliferative activity in human pancreatic cancer cells

Cited by 28 publications

References 50 publications

Vanadium(V/IV)–Transferrin Binding Disrupts the Transferrin Cycle and Reduces Vanadium Uptake and Antiproliferative Activity in Human Lung Cancer Cells

Vanadium(V/IV)–Transferrin Binding Disrupts the Transferrin Cycle and Reduces Vanadium Uptake and Antiproliferative Activity in Human Lung Cancer Cells

Kinetic Studies of Sodium and Metforminium Decavanadates Decomposition and In Vitro Cytotoxicity and Insulin- Like Activity

Synthesis, Crystal Structure, and Computational Methods of Vanadium and Copper Compounds as Potential Drugs for Cancer Treatment

Contact Info

Product

Resources

About