Physiological roles of peroxido-vanadium complexes: Leitmotif as their signal transduction pathway

Matsugo, Seiichi; Kanamori, Kan; Sugiyama, Hironori; Makino, Hírofumi; Takamura, Toshinari

doi:10.1016/j.jinorgbio.2015.02.008

Cited by 16 publications

(12 citation statements)

References 60 publications

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“…V V species cause intracellular inhibition of protein tyrosine phosphatases (PTPs), either through reversible binding to Cys residues in the enzyme active centers or via strongly oxidizing peroxido vanadates (formed in situ) that irreversibly oxidize Cys residues to sulfinic acid (Scheme ) . Both events lead to increased phosphorylation of regulatory proteins to enhance cell signaling, including insulin signaling …”

Section: Vanadium Complexes As Pro‐drugssupporting

confidence: 65%

“…It remains to be established whether V III ‐Tf is taken into cells by the same receptor‐mediated endocytosis mechanism as Fe III ‐Tf ( C , Scheme ), since recent studies showed that a Cr III ‐Tf analog is excluded from cells due to disrupted interactions with the Tf receptor on the cell surface . V V species cause intracellular inhibition of protein tyrosine phosphatases (PTPs), either through reversible binding to Cys residues in the enzyme active centers or via strongly oxidizing peroxido vanadates (formed in situ) that irreversibly oxidize Cys residues to sulfinic acid (Scheme ) . Both events lead to increased phosphorylation of regulatory proteins to enhance cell signaling, including insulin signaling …”

Section: Vanadium Complexes As Pro‐drugsmentioning

confidence: 99%

“…Vanadium(V) peroxido complexes are more potent PTP inhibitors than vanadate in cell‐free systems, due to irreversible oxidation of Cys residues at enzyme active sites (Scheme ) . In vitro biological activities of V V peroxido complexes are more controversial, due to their unknown stability in cell culture media .…”

Section: Reactivity and Anti‐proliferative Activity Of Vanadium Complmentioning

confidence: 99%

“…[28] V V speciesc ause intracellular inhibition of protein tyrosine phosphatases( PTPs), either through reversi-ble binding to Cys residues in the enzymea ctive centers or via strongly oxidizing peroxido vanadates (formedinsitu) that irreversibly oxidize Cys residues to sulfinic acid (Scheme 1). [4,29,30] Both events lead to increased phosphorylation of regulatory proteins to enhance cell signaling, including insulin signaling. [4,29,30] This well-established extracellularr eactivity of anti-diabetic V drugs (Scheme 1) is often ignored in studies of anti-cancer V drugs that are generally assumedt oe nter cells intact, [2,3] despite little experimental evidencet os upport this claim (see Section2).…”

Section: Vanadium Complexes As Pro-drugsmentioning

confidence: 99%

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Stabilities and Biological Activities of Vanadium Drugs: What is the Nature of the Active Species?

Levina

Lay

2017

Chemistry An Asian Journal

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Diverse biological activities of vanadium(V) drugs mainly arise from their abilities to inhibit phosphatase enzymes and to alter cell signaling. Initial interest focused on anti-diabetic activities but has shifted to anti-cancer and anti-parasitic drugs. V-based anti-diabetics are pro-drugs that release active components (e.g., H VO ) in biological media. By contrast, V anti-cancer drugs are generally assumed to enter cells intact; however, speciation studies indicate that nearly all drugs are likely to react in cell culture media during in vitro assays and the same would apply in vivo. The biological activities are due to V and/or V reaction products with cell culture media, or the release of ligands (e.g., aromatic diimines, 8-hydroxyquinolines or thiosemicarbazones) that bind to essential metal ions in the media. Careful consideration of the stability and speciation of V complexes in cell culture media and in biological fluids is essential to design targeted V-based anti-cancer therapies.

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Section: Vanadium Complexes As Pro‐drugssupporting

confidence: 65%

Section: Vanadium Complexes As Pro‐drugsmentioning

confidence: 99%

Section: Reactivity and Anti‐proliferative Activity Of Vanadium Complmentioning

confidence: 99%

Section: Vanadium Complexes As Pro-drugsmentioning

confidence: 99%

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Stabilities and Biological Activities of Vanadium Drugs: What is the Nature of the Active Species?

Levina

Lay

2017

Chemistry An Asian Journal

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“…In addition to the widely known therapeutic properties of oxidovanadium(V) compounds, such as their insulin-mimetic activity, there is a growing interest in vanadium compounds as potential therapeutic agents for the treatment of cancer [15][16][17]. A complex of this metal with an o-HVa-derived Schiff base ligand has been determined to bind to CT-DNA in a nonclassical intercalative mode and to possess a strong affinity with the BSA protein, inducing conformational changes [18].…”

Section: Scheme 1 Inhovamentioning

confidence: 99%

A novel oxidovanadium(V) compound with an isonicotinohydrazide ligand. A combined experimental and theoretical study and cytotoxity against K562 cells

et al. 2017

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A novel oxidovanadium(V) compound with an isonicotinohydrazide ligand. A combined experimental and theoretical study and cytotoxity against K562 cells. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Bis(acetylacetonato)-oxidovanadium(IV) and sodium metavanadate inhibit cell proliferation via ROS-induced sustained MAPK/ERK activation but with elevated AKT activity in human pancreatic cancer AsPC-1 cells

Hong

Yang

2016

J Biol Inorg Chem

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In this study, the antiproliferative effect of bis(acetylacetonato)-oxidovanadium(IV) and sodium metavanadate and the underlying mechanisms were investigated in human pancreatic cancer cell line AsPC-1. The results showed that both exhibited an antiproliferative effect through inducing G2/M cell cycle arrest and can also cause elevation of reactive oxygen species (ROS) levels in cells. Moreover, the two vanadium compounds induced the activation of both PI3K/AKT and MAPK/ERK signaling pathways dose- and time-dependently, which could be counteracted with the antioxidant N-acetylcysteine. In the presence of MEK-1 inhibitor, the degradation of Cdc25C, inactivation of Cdc2 and accumulation of p21 were relieved. However, the treatment of AKT inhibitor did not cause any significant effect. Therefore, it demonstrated that the ROS-induced sustained MAPK/ERK activation rather than AKT contributed to vanadium compounds-induced G2/M cell cycle arrest. The current results also exhibited that the two vanadium compounds did not induce a sustained increase of ROS generation, but the level of ROS reached a plateau instead. The results revealed that an intracellular feedback loop may be against the elevated ROS level induced by vanadate or VO(acac), evidenced by the increased GSH content, the unchanged level at the expression of antioxidant enzymes. Therefore, vanadium compounds can be regarded as a novel type of anticancer drugs through the prolonged activation of MAPK/ERK pathway but retained AKT activity. The present results provided a proof-of-concept evidence that vanadium-based compounds may have the potential as both antidiabetic and antipancreatic cancer agents to prevent or treat patients suffering from both diseases.

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Physiological roles of peroxido-vanadium complexes: Leitmotif as their signal transduction pathway

Cited by 16 publications

References 60 publications

Stabilities and Biological Activities of Vanadium Drugs: What is the Nature of the Active Species?

Stabilities and Biological Activities of Vanadium Drugs: What is the Nature of the Active Species?

A novel oxidovanadium(V) compound with an isonicotinohydrazide ligand. A combined experimental and theoretical study and cytotoxity against K562 cells

Bis(acetylacetonato)-oxidovanadium(IV) and sodium metavanadate inhibit cell proliferation via ROS-induced sustained MAPK/ERK activation but with elevated AKT activity in human pancreatic cancer AsPC-1 cells

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