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Geldanamycin Induces Cell Cycle Arrest in K562 Erythroleukemic Cells
Author(s) -
Kim Hong Ro,
Lee Chang Hoon,
Choi Yung Hyun,
Kang Ho Sung,
Kim Han Do
Publication year - 1999
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1080/713803539
Subject(s) - geldanamycin , cell cycle checkpoint , microbiology and biotechnology , chemistry , k562 cells , cell cycle , cancer research , hsp90 , cell , biology , biochemistry , heat shock protein , gene
Geldanamycin (GA), a benzoquinone ansamycin, is one of the specific inhibitors of 90‐kDa heat shock protein and induces growth inhibition and apoptosis in certain cancer cell lines. We have investigated the mechanism of GA‐induced growth inhibition in K562 erythroleukemic cells. DNA flow‐cytometric analysis indicated that GA‐induced growth arrest was associated with G2/M phase arrest of the cell cycle. GA treatment down‐regulated the expression of cyclin B1 and inhibited phosphorylation of Cdc2 protein, both key regulatory proteins at the G2/M boundary. GA also markedly inhibited the Cdc2 kinase activity, which may be in part a result of up‐regulation of p27KIP1 by GA. The present results suggest a novel mechanism that p27KIP1 could be involved in the regulation of G2 to M phase transition.