Antitumoral activivity of a series of oxidovanadium(IV)-flavonoid complexes. Apoptotic signalling pathways

E. G. FERRER; L. NASO; M. VALCARCEL; P. VILLACÉ; M. ROURA; D. KORTAZAR; C. SALADO; P.A.M. WILLIAMS

Granada

Congreso; 11th European Biological Inorganic Chemistry Conference (EUROBIC11); 2012

Universidad de Granada

Most flavonoids are very powerful antioxidants with the ability to prevent numerous diseases. Besides, oxovanadium(IV) complexes are well documented to have therapeutic applications. Inorganic coordination compounds formed with this biometal and flavonoids can be crucial for the improvement of their physiological effects, such as antitumoral and antioxidant ones, among others. Therefore, we have synthesized and characterized coordination complexes of oxovanadium(IV) and the flavonoids quercetin, hesperidin, silibinin and chrysin in order to study their behavior in biological systems.[1] We have previously reported the antiproliferative effects of some of these compounds on two osteoblastic cell lines in culture (MC3T3E1 and UMR106), and their effects as antioxidant agents in vitro and in the cells. Herewith, we present an extended study on the antitumoral activity on some breast cancer cultured cell lines (MDA-MB231, MDA-MB468, BT474, T47D and SKBR3) which was determined by the cell viability assay. Moreover, a new compound formed between oxovanadium(IV) and morin was included in the series. Besides, we have studied the probable pathway by which the complexes induced apoptosis in the MDA-MB231 breast cancer cell line using different tests (caspase 3/7 and mitotic arrest assay, and the high content cytotoxiciy assays: measurement of intracellular ROS content and mitochondrial membrane potential (using CM-H2DCFDA and TMRM probes), and active caspase 3/7 and histone phoshorylation by immunoyhistochemistry. Both the ligands and the metal did not show significantly alterations on these parameters. These tests allowed us to conclude that the formation of VO (IV) complexes enhanced the antiproliferative effects of chrysin and silibinin by the caspase 3/7 activation and the microtubule structural changes pathway in the MDA-MB-231 breast cancer cells. [2]