Decoding the antitumor activity of VO-compounds in a human osteosarcoma model: the role of FAK and caspases on cell death pathways

LEON I.E

Simposio; V11 International Simposium of Vanadium; 2018

Metal-based drugs have a wide spectrum of pharmacological activities against different pathologies, including diabetes and cancer 1. In this way, vanadium compounds were studied in recent years by considering them as a representative of a new class of non-platinum metallodrugs. However, studies on cell signaling pathways related to vanadium compounds have scarcely been reported and 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 the intracellular signaling pathways promoted by an oxovanadium(IV)complexes with clioquinol [VO(CQ2)] and chrysin [VO(chrysin)2] on a human osteosarcoma cell line (MG-63).Herein are reported, for the first time, the antitumor properties of these compounds and the relative abundance of 224 proteins (which are involved in most of the common intracellular pathways) to identify novel targets of the studied complexes. Besides, full-length human recombinant AKT1 kinase and FAK were produced using an IVTT system to evaluate the variation of relative tyrosin-phosphorylation levels caused by these compounds. The results of the differential protein expression levels reveal several up-regulated proteins such as CASP3, CASP6, CASP7, CASP10, CASP11, Bcl-x, DAPK and down-regulated ones, such as PKB/AKT, DIABLO, among others. Moreover, cell signaling pathways related to the PKC, FAK and AP2 family have been identified in both treatments suggesting the crucial antitumoral role of vanadium compounds. On the other hand, [VO(chrysin)2] reduced the Tyr/GST ratio of FAK and reduced Tyr/GST ratio of AKT1. These results demonstrating the importance of inactivation of the FAK and AKT pathway in the antitumor effects of these compounds. Finally, these results indicate that both compounds are promising candidates with potential anticancer activity providing new insights into the design of vanadium complexes as potential anticancer agents