Vanadium and bone cancer treatment: In silico and in vitro analysis of FAK/MMP signaling axis inhibition by VO-clioquinol on 2D and 3D human osteosarcoma cancer models

LEON IE

Simposio; V12 International Simposium of Vanadium; 2021

Vanadium is an ultratrace element present in higher plants and animals1 . The therapeutic actions of vanadium convert its class of drugs into possible pharmaceutical agents to be used in the treatment of many pathologies, including neurodegenerativediseases, diabetes, and cancer 2. Therefore, vanadium complexes have recently emerged as non-platinum antitumor agents 3. Nevertheless, a few challenges remain for the useand application of this kind of compound, such as lack of specificity, poor absorption, and unknown mechanism of action, among others. So, the study of novel mechanisms of action of vanadium compounds is very relevant to elucidating the role and importance of these types of compounds as anticancer and antimetastatic agents. As part of a larger project, this research deals with deciphering the mode of interaction between one oxidovanadium(IV) complex and clioquinol [VO(clioquinol)2], VO(CQ)2,) and Focal Adhesion Kinase (FAK). In particular, the present study mainly focuses on elucidating the relationship between the FAK regulation, matrix metalloproteinase (MMP) activity and antimetastatic effects of the complex in 2D and 3D human osteosarcoma cell models.The results showed that VO(CQ)2 is located near to the activation loop of the kinase domain and establishes interactions with residues in the ATP binding site. Moreover, the compound reduced cell migration and the activity of MMP-2 and MMP-9 on 2D and 3D human bone cancer cell models. Taken together, these results indicate that VO(CQ)2 is a promising candidate with potential antimetastatic activity against osteosarcoma cells, so it would be interesting to test this complex in further in vivo assays for cancer treatment.