Deciphering the effect of an oxovanadium( iv ) complex with the flavonoid chrysin (VOChrys) on intracellular cell signalling pathways in an osteosarcoma cell line

Abstract

Vanadium complexes were studied during recent years and considered as a representative of a newclass of non-platinum metal antitumor agents in combination with their low toxicity. However, a fewchallenges still remain in the discovery of new molecular targets for these novel metal-based drugs. Thestudy of cell signaling pathways related to vanadium drugs, which is highly critical for identifying specific Q4targets that play an important role in the antitumor activity of vanadium compounds, is scarce. Thisresearch deals with the alterations in intracellular signaling pathways promoted by an oxovanadium(IV)complex with the flavonoid chrysin [VO(chrysin)2EtOH]2 (VOChrys) in a human osteosarcoma cell line(MG-63). Herein we report for the first time the effect of [VO(chrysin)2EtOH]2 on the relative abundance Q5of 224 proteins, which are involved in the most common intracellular pathways. Besides, full-lengthhuman recombinant (FAK and AKT1) kinases are produced using an in situ IVTT system and then wehave evaluated the variation of relative tyrosine-phosphorylation levels caused by the[VO(chrysin)2EtOH]2 compound. The results of the differential protein expression levels reveal thatseveral proteins such as PKB/AKT, PAK, DAPK, Cdk 4, 6 and 7, FADD, AP2, NAK, and JNK, among others,were altered. Moreover, cell signaling pathways related to the PTK2B, FAK, PKC families suggests an Q6important role associated with the antitumor activity of [VO(chrysin)2EtOH]2 was demonstrated. Finally,the effect of this compound on in situ expressed FAK and AKT1 is validated by determining thephosphorylation level, which decreased in the former and increased in the latter.