Enhancement of oncolytic virotherapy by vanadium(V) dipicolinates

Bergeron, Anabel; Kostenkova, Kateryna; Selman, Mohammed; Murakami, Heide A.; Owens, Elizabeth; Haribabu, Naveen; Arulanandam, Rozanne; Diallo, Jean-Simon; Crans, Debbie C.

doi:10.1007/s10534-019-00200-9

Cited by 23 publications

(12 citation statements)

References 60 publications

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“…In contrast to suggestions in the literature, ,, V(V/IV)–Tf binding prevents cellular V uptake through the Tf–TfR1 uptake pathway under normoxic conditions, due to the inability of V(V/IV)–Tf to complete the Tf cycle, although this does not exclude the role of V(III)–Tf formed under hypoxic and/or reducing conditions. , A decrease in V(V/IV) cellular uptake in the presence of Tf leads to a dramatic decrease in its antiproliferative activity. This factor has to be taken into account in the development of medicinal V(V) and V(IV) complexes, ,− since such complexes are likely to dissociate fully or partially in the blood with the formation of V(V/IV)–Tf adducts. − , The development of metal complexes that can withstand the protein binding in an extracellular environment to enable them to enter cells intact and to release active components within the cells is a likely prerequisite to their anticancer activity. ,, An improved understanding of the roles of V(V/IV) binding to Tf and other biomolecules is required to facilitate the development of promising novel applications of V(V/IV) complexes, including activation of oncolytic viruses, , treatment of neurodegenerative disorders, , and intratumoral injections for the treatment of unresectable cancers …”

Section: Discussionmentioning

confidence: 99%

“…to enter cells intact and to release active components within the cells is a likely prerequisite to their anticancer activity. 13,78,80 An improved understanding of the roles of V(V/IV) binding to Tf and other biomolecules is required to facilitate the development of promising novel applications of V(V/IV) complexes, including activation of oncolytic viruses, 83,84 treatment of neurodegenerative disorders, 85,86 and intratumoral injections for the treatment of unresectable cancers. 87 ■ ASSOCIATED CONTENT * sı Supporting Information…”

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confidence: 99%

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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.

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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.

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Section: Discussionmentioning

confidence: 99%

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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.

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“…[11][12][13][14] Our group has identified sodium orthovanadate (vanadate) and other vanadium-based compounds as being capable not only of attenuating the antiviral IFN-1 response, but also simultaneously increasing proinflammatory activity through type II interferon (IFN-2) signals when co-administrated with the oncolytic vesicular stomatitis virus (VSVD51). 15,16 In addition to reducing IFN-1 responses, vanadate treatment increases virusinduced proinflammatory cytokines including interferon-beta (IFNb), tissue necrosis factor alpha (TNF-ɑ), and interleukin 6 (IL-6). We have previously shown that the effect of vanadate on the IFN-1 and IFN-2 response correlates with the accumulation of phosphorylated STAT1 (signal transducer and activation of transcription) transcription factor in the nucleus and reduced STAT2 expression/ activation.…”

Section: Introductionmentioning

confidence: 99%

Dependency of EGFR activation in vanadium-based sensitization to oncolytic virotherapy

Wong

Bergeron

Alluqmani

et al. 2022

Molecular Therapy - Oncolytics

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“…Both vanadate and vanadyl sulfate as well as one coordination complex, bis(ethylmaltolato)oxovanadium(IV), have been investigated for potential treatment against diabetes in Phase I and II clinical trials [69,74,75]. Vanadium coordination complexes also have activities as anticancer compounds [76,77], and recently both salts and select complexes were found to enhance an oncolytic virus, VSV∆51, in combatting cancers that are resistant to existing therapeutics [78,79].…”

Section: Vanadium (V)mentioning

confidence: 99%

The First-Row Transition Metals in the Periodic Table of Medicine

Cleave

Crans

2019

Inorganics

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In this manuscript, we describe medical applications of each first-row transition metal including nutritional, pharmaceutical, and diagnostic applications. The 10 first-row transition metals in particular are found to have many applications since there five essential elements among them. We summarize the aqueous chemistry of each element to illustrate that these fundamental properties are linked to medical applications and will dictate some of nature’s solutions to the needs of cells. The five essential trace elements—iron, copper, zinc, manganese, and cobalt—represent four redox active elements and one redox inactive element. Since electron transfer is a critical process that must happen for life, it is therefore not surprising that four of the essential trace elements are involved in such processes, whereas the one non-redox active element is found to have important roles as a secondary messenger.. Perhaps surprising is the fact that scandium, titanium, vanadium, chromium, and nickel have many applications, covering the entire range of benefits including controlling pathogen growth, pharmaceutical and diagnostic applications, including benefits such as nutritional additives and hardware production of key medical devices. Some patterns emerge in the summary of biological function andmedical roles that can be attributed to small differences in the first-row transition metals.

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Enhancement of oncolytic virotherapy by vanadium(V) dipicolinates

Cited by 23 publications

References 60 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

Dependency of EGFR activation in vanadium-based sensitization to oncolytic virotherapy

The First-Row Transition Metals in the Periodic Table of Medicine

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