Effects of the tumor inhibitor IKP-104, a 4(1H)-pyridinone derivative, on cytoskeletal microtubules of cultured tumor cells

The effects of IKP-104, a 4(1H)-pyridinone derivative, on the mitotic profile and cytoskeletal microtubule dynamics of cultured B16 melanoma cells were examined in order to investigate the mechanism of its antitumor activity. The exposure to IKP-104 caused accumulation of cells in abnormal metaphase with chromosomes scattered within the cytoplasm and induced polyploid and multinucleate cells as detected by differential staining microscopy with brilliant blue R and safranin O. An immunofluorescence study with monoclonal anti-alpha-tubulin antibody revealed that IKP-104 diminished cytoskeletal microtubules of both interphase and mitotic cells, resulting in induction of a few fragments resembling "microtubular bundles" induced by vinblastine (VLB). These results indicated that IKP-104 arrests cells in the mitotic phase by inhibition of polymerization and induction of depolymerization of cytoskeletal microtubules, similarly to VLB.