Inhibition of nucleolar function and morphological change by adriamycin associated with heat shock protein 70 accumulation.
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 microM 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.
Abe
T
T
Department of Biochemistry, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Fukuoka.
Fukamachi
Y
Y
Kanazawa
Y
Y
Furukawa
H
H
Shimizu
K
K
Hirano
T
T
Kasai
H
H
Kashimura
M
M
Higashi
K
K
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002466:Cell Nucleolus / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000187:drug effects / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D010084:Oxidation-Reduction
D000903:Antibiotics, Antineoplastic; D004273:DNA, Neoplasm; D018840:HSP70 Heat-Shock Proteins; D004317:Doxorubicin