Jump to main content
Jump to site search


Decoding the anticancer activity of VO-Clioquinol compound: mechanism of action and cell death pathways in human osteosarcoma cells

Abstract

Vanadium compounds were studied during recent years to be considered as a representative of a new class of non-platinum metal anticancer drugs. However, a few challenges are still remaining for the discovery of new molecular targets of these new metallodrugs. The study of cell signaling pathways related to vanadium compounds are scarcely reported and so far this information is highly critical for identifying novel targets that play a key role in the antitumor actions of vanadium complexes. This research deals with the alterations in intracellular signaling pathways promoted by an oxovanadium(IV) complex with the clioquinol (5-Chloro-7-iodo-8-quinolinol), VO(CQ)2, on a human osteosarcoma cell line (MG-63). Herein it is reported, for the first time, the antitumor properties of the VO(CQ)2 and the relative abundance of 224 proteins (which are involved in most of the common intracellular pathways) to identify novel targets of the studied complex. Besides, the full-length human recombinant AKT1 kinase was produced by using an IVTT system to evaluate the variation of relative tyrosin-phosphorylation levels caused by this compound. The results of the differential protein expression levels reveal several proteins up-regulated such as CASP3, CASP6, CASP7, CASP10, CASP11, Bcl-x, DAPK and down-regulated such PKB/AKT, DIABLO, among others. Moreover, cell signaling pathways involved in several altered pathways related to PKC and AP2 family have been identified in both treatment (2.5 and 10 µM) suggesting the crucial antitumoral role of VO(CQ)2. Finally, it has been demonstrated that this compound (10 µM, 6h) triggers a decreasing in 2 fold of AKT1 in situ expression.

Back to tab navigation
Please wait while Download options loads

Supplementary files

Publication details

The article was received on 08 Mar 2017, accepted on 26 Apr 2017 and first published on 26 Apr 2017


Article type: Paper
DOI: 10.1039/C7MT00068E
Citation: Metallomics, 2017, Accepted Manuscript
  •   Request permissions

    Decoding the anticancer activity of VO-Clioquinol compound: mechanism of action and cell death pathways in human osteosarcoma cells

    I. Leon, P. Díez, E. J. Baran, S. B. Etcheverry and M. Fuentes, Metallomics, 2017, Accepted Manuscript , DOI: 10.1039/C7MT00068E

Search articles by author