The chemistry and biology of vanadium compounds in cancer therapeutics

A diverse spectrum of vanadium compounds have arisen, over the past years, as potential therapeutic agents for the treatment of malignancies. Poised to delineate the role of that transition metal ion in the biology of antitumor activity, vanadium complex species are classified in families, encompassing among others organometallic vanadocene V(C5H5)(2), oxidovanadium (V(IV)O)-containing compounds, binary and ternary peroxidovanadates and vanadium-peroxido-betaine complexes, and polyoxovanadate species. Their physicochemical nature reveals the structural integrity of the corresponding V(II), V(IV) and V(V) vanadoforms and exemplifies the distinct vanadium chemical reactivity patterns leading to discrete species likely to favor physiological and biochemical compatibility in a (sub)cellular environment. The ensuing analysis of the biological activity of these vanadoforms unravels specific roles for vanadium, commensurate with its physicochemical nature and properties. Invariably, it appears that vanadium suppresses growth and the spread of tumors by (a) inhibiting tumor cell proliferation and inducing apoptosis, and (b) limiting invasion and the metastatic potential of neoplastic cells. The prospect of vanadium's involvement in redox-active ROS-RNS associated apoptotic processes, interactions with miRNA, autophagy, anoikis mechanistic processes and cell differentiation capacities, individually and/or collectively contributing to the demise of cancer cells, denotes the potential of that metal ion as a future anticancer metallodrug. Concurrent consideration of both the chemical and biological attributes of the existing vanadoforms set the stage for the design and synthetic strategies leading to vanadium species aspiring to promote biological anticancer activity with effectiveness, selectivity and specificity. The molecular events associated with the advent of such vanadium compounds set the future challenges of this interdisciplinary field of bioinorganic chemistry and are expected to shape the prospect of achieving effective antitumor vanadodrugs. (C) 2015 Elsevier B.V. All rights reserved.