Bis(4,7-dimethyl-1,10-phenanthroline) sulfatooxovanadium(IV) as a novel antileukemic agent with matrix metalloproteinase inhibitory activity

We have examined the in vitro anticancer activity of METVAN [bis(1,7-dimeth yl-1,10 phenanthroline) sulfatooxovanadium(IV); VO(SO4)(Me-2-Phen)(2)] agai nst acute lymphoblastic leukemia (ALL; NALM-6 and MOLT-3), acute myeloid le ukemia (AML; HL-60), Hodgkin's disease (HS445), and multiple myeloma (ARH-7 7, U266BL, and MS-SULTAN) cell lines as well as primary leukemic cells from patients with ALL, AML, and chronic acute myeloid leukemia (CML). METVAN i nduced apoptosis in NALM-6, MOLT-3, and HL-60 cells in a concentration-depe ndent fashion with EC,, values of 0.19 +/- 0.03 muM, 0.19 +/- 0.01 muM, and 1.1 +/- 0.2 muM, respectively. METVAN induced apoptosis at law micromolar concentrations in primary leukemic cells from patients with ALL, AML, and C ML. METVAN inhibited the constitutive expression of matrix metalloproteinas e (MMP)-9 protein and its gelatinolytic activity in HL-60 cells and MMP-2 a s well as MMP-9 gelatinolytic activities in leukemic cells from ALL, AML, a nd CML patients. Furthermore, METVAN inhibited the leukemic cell adhesion t o the extracellular matrix proteins laminin, type IV collagen, vitronectin, and fibronectin and the invasion through Matrigel matrix. Further preclini cal development of METVAN map provide the basis for the development of more effective chemotherapy programs.