Geldanamycin Induces Cell Cycle Arrest in K562 Erythroleukemic Cells

• Published in: IUBMB life 1999-10, Vol.48 (4), p.425-428
• Main Authors: Kim, Hong Ro, Lee, Chang Hoon, Choi, Yung Hyun, Kang, Ho Sung, Kim, Han Do
• Format: Article
• Language: English
• Subjects: Antibiotics, Antineoplastic - pharmacology; Benzoquinones; CDC2 Protein Kinase - antagonists & inhibitors; CDC2 Protein Kinase - metabolism; Cell Cycle - drug effects; Cell Cycle Proteins; Cell Division - drug effects; Cyclin B - biosynthesis; Cyclin B1; Cyclin-Dependent Kinase Inhibitor p27; G2 Phase - drug effects; G2m Arrest; Geldanamycin; Growth Inhibitors - pharmacology; Humans; K562 Cells - pathology; Lactams, Macrocyclic; Leukemia, Erythroblastic, Acute - pathology; Microtubule-Associated Proteins - biosynthesis; Mitosis - drug effects; P27kip1; Phosphorylation; Quinones - pharmacology; Tumor Suppressor Proteins; Up-Regulation - drug effects
• ISSN: 1521-6543; 1521-6551
• DOI: 10.1080/713803539

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.