The effect of mitoxantrone as an anticancer drug on hepatocytes nuclei and chromatin: Selective release of histone proteins

OBJECTIVES: Mitoxantrone is an anticancer drug widely used in the treatment of various cancers. In the present study the effect of mitoxantrone on chromatin proteins of intact hepatocytes nuclei was investigated and compared with soluble chromatin. MATERIALS AND METHODS: UV/Vis spectroscopy, SDS polyacrylamide gel electrophoresis, and western bolting were used. RESULTS: The results show that exposure of intact nuclei to various concentrations of mitoxantrone resulted in the release of histone H1 family proteins, H1 and H1°, in a dose-dependent manner but not core histones and high mobility group proteins. Western blot analysis using antiserum against histones H1 and H1° revealed cross-reactivity and confirmed the result. Spectroscopy results showed that mitoxantrone binds to nuclear components and reduces the absorbances at 608 and 400 nm. The binding isotherms revealed cooperative binding with one binding site. CONCLUSION: From the results it is suggested that mitoxantrone binds to intact nuclei and chromatin with different affinities and linker DNA can be considered as a main binding site for mitoxantrone at the nuclei level.