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Inhibition of Nucleolar Function and Morphological Change by Adriamycin Associated with Heat Shock Protein 70 Accumulation
Authors:Tetsuya Abe  Yukiyo Fukamachi  Yohsuke Kanazawa  Hiroshi Furukawa  Kenji Shimizu  Takeshi Hirano  Hiroshi Kasai  Masamichi Kashimura  Ken Higashi
Affiliation:Department of Biochemistry, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, Fukuoka 807;Department of Anatomy, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, Fukuoka 807;Department of Environmental Oncology, Institute of Industrial Ecology, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, Fukuoka 807;Department of Obstetrics and Gynecology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, Fukuoka 807
Abstract:Adriamycin (ADR) has been considered to target mainly DNA metabolism in the nucleus. Recently, we observed the nuclear translocation of heat shock protein 70 (HSP70) after ADR treatment. We examined which intranuclear changes might be related to this alteration of HSP70 localization. We found considerable alternations in the nucleolar morphology and function in ADR-treated tumor cells, i.e., a ring-shaped segregation of granular components of almost all nucleoli and a dramatic reduction of nucleolar 45S ribosomal precursor RNA biosynthesis in HeLa cells exposed to 100 μ M ADR for 2 h. Concomitantly with these changes, HSP70 was concentrated into the nucleoli, as in the case of heat shock treatment. These results indicate a novel anticancer effect of ADR via the suppression of cellular protein biosynthesis, in addition to its effect on DNA.
Keywords:Adriamycin    HSP70    Nucleolus    DNA damage    HeLa cells
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