Thiazolidinedione anti-cancer activity: Is inhibition of microtubule assembly implicated?

An hypothesis is presented which seeks to explain the anti-cancer activity of thiazolidinediones (TZDs), a class of drugs currently used to treat type 2 diabetes mellitus. Empirical data from the scientific literature is used to support the hypothesis that TZDs are inhibitors of microtubule assembly. The similarities between the affects of TZDs on cellular processes and known inhibitors of tubulin polymerization are identified. Similarities between TZDs and currently used inhibitors of microtubule assembly, such as cell cycle arrest in G1 phase, anti-angiogenesis activity, and inhibition of cell motility, are striking. In addition to the similarities in biological function, certain molecular structure similarities are also identified. The possibility that TZDs inhibit the polymerization of actin is presented as an alternative interpretation of the available data. Finally suggestions for testing the hypothesis, by using commercially available tubulin polymerization assays and fluorescence based binding assays, as well as isothermal titration calorimetry, are given. Considering TZD position as third-line therapy for treatment of type 2 diabetes mellitus and the potential loss of market share to newly introduced inhalable insulin, a better understanding of TZD anti-cancer activity may lead to revival for this drug class in cancer treatment.