Hsp90 inhibitors cause G2/M arrest associated with the reduction of Cdc25C and Cdc2 in lung cancer cell lines

• Published in: Journal of cancer research and clinical oncology 2006-03, Vol.132 (3), p.150-158
• Main Authors: SENJU, Megumi, SUEOKA, Naoko, SATO, Akemi, IWANAGA, Kentaro, SAKAO, Yukinori, TOMIMITSU, Shinji, TOMINAGA, Masaki, IRIE, Koji, HAYASHI, Shinichiro, SUEOKA, Eisaburo
• Format: Article
• Language: English
• Subjects: Antineoplastic agents; Apoptosis - drug effects; Apoptosis - physiology; Benzoquinones - pharmacology; Biological and medical sciences; Blotting, Western; CDC2 Protein Kinase - biosynthesis; CDC2 Protein Kinase - drug effects; cdc25 Phosphatases - biosynthesis; cdc25 Phosphatases - drug effects; Cell Cycle Proteins - biosynthesis; Cell Cycle Proteins - drug effects; Cell Line, Tumor; Female; G2 Phase - drug effects; HSP90 Heat-Shock Proteins - antagonists & inhibitors; HSP90 Heat-Shock Proteins - biosynthesis; HSP90 Heat-Shock Proteins - drug effects; Humans; Immunohistochemistry; Immunoprecipitation; Inhibitor drugs; Lactams, Macrocyclic - pharmacology; Lung cancer; Lung Neoplasms - metabolism; Male; Medical sciences; Oncology; Pharmacology. Drug treatments; Pneumology; Proteins; Tumors of the respiratory system and mediastinum
• ISSN: 0171-5216; 1432-1335
• DOI: 10.1007/s00432-005-0047-7

Hsp90, a molecular chaperone, is involved in folding, assembly, maturation, and stabilization of the client proteins which regulate survival of cancer cells, and thus Hsp90 inhibitors may be potential molecular targeting agents for cancer treatment. We investigated whether Hsp90 inhibitors have therapeutic value in lung cancer. First, expression levels of Hsp90 in lung cancer cells were examined by western blotting and immunohistochemical analyses. Next, the effect of Hsp90 inhibitors, geldanamycin and 17-allylaminogeldanamycin (17-AAG), on lung cancer cell growth was examined. Remarkable high expression of Hsp90 protein in lung cancer cell lines and a more intense signal for Hsp90 by immunohistochemistry in males, patients with smoking index over 600, and squamous cell carcinoma were observed. Both Hsp90 inhibitors dose dependently inhibited the growth of lung cancer cell lines and induced G2/M arrest concomitant with decreased protein levels of Cdc25C and Cdc2. Moreover, combination of an Hsp90 inhibitor and irradiation had an additive effect on cell growth inhibition and reduction of Cdc25C and Cdc2 protein levels. Hsp90 inhibitor is thus a therapeutic tool for lung cancer based on its target proteins, which are involved in tumor progression and antiproliferative activity in lung cancer cells.