Vanadium in cancer treatment.
Vanadium compounds exert preventive effects against chemical carcinogenesis on animals, by modifying, mainly, various xenobiotic enzymes, inhibiting, thus, carcinogen-derived active metabolites. Studies on various cell lines reveal that vanadium exerts its antitumor effects through inhibition of cellular tyrosine phosphatases and/or activation of tyrosine phosphorylases. Both effects activate signal transduction pathways leading either to apoptosis and/or to activation of tumor suppressor genes. Furthermore, vanadium compounds may induce cell-cycle arrest and/or cytotoxic effects through DNA cleavage and fragmentation and plasma membrane lipoperoxidation. Reactive oxygen species generated by Fenton-like reactions and/or during the intracellular reduction of V(V) to V(IV) by, mainly, NADPH, participate to the majority of the vanadium-induced intracellular events. Vanadium may also exert inhibitory effects on cancer cell metastatic potential through modulation of cellular adhesive molecules, and reverse antineoplastic drug resistance. It also possesses low toxicity that, in combination with the synthesis of new, more potent and better tolerated complexes, may establish vanadium as an effective non-platinum, metal antitumor agent.
Evangelou
Angelos M
AM
Faculty of Medicine, Laboratory of Physiology, University of Ioannina, Ioannina, Greece. aevaggel@cc.uoi.gr
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004351:Drug Resistance; D006801:Humans; D009362:Neoplasm Metastasis / Q000517:prevention & control; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009942:Organometallic Compounds / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects; D010599:Pharmacokinetics; D014639:Vanadium / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity
D009942:Organometallic Compounds; D014639:Vanadium