Inhibition of Nucleolar Function and Morphological Change by Adriamycin Associated with Heat Shock Protein 70 Accumulation |
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Authors: | Tetsuya Abe Yukiyo Fukamachi Yohsuke Kanazawa Hiroshi Furukawa Kenji Shimizu Takeshi Hirano Hiroshi Kasai Masamichi Kashimura Ken Higashi |
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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 |
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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. |
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Keywords: | Adriamycin HSP70 Nucleolus DNA damage HeLa cells |
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