Effect of staurosporine on suppression of heat shock gene expression and thermotolerance development in HT-29 cells.
Staurosporine, an inhibitor of protein kinase C (PKC), was selected to determine the effect of drug on the development of thermotolerance and the expression of heat shock protein genes. Experiments were carried out with human colon carcinoma HT-29 cells. Heat shock induction consisted of 45 degrees C for 15 min and subsequent incubation at 37 degrees C for 6 h. Thermotolerance developed rapidly, reached its maximum at 6 h after heat shock, and decayed gradually. At maximal thermal resistance, thermotolerance ratio at 10% isosurvival was 3.8. The development of thermotolerance was markedly inhibited by treatment with staurosporine (0.1-5.0 micrograms/ml). Exposure to 1.0 and 5.0 micrograms/ml staurosporine reduced thermotolerance ratio to 1.8 and 1.1 respectively. Further, the levels of heat shock protein genes (HSP 28 and 70) encoding mRNA were equally reduced by the drug treatment. These results suggest that PKC is involved in the regulation of heat shock gene expression and development of thermotolerance.
Department of Radiation Oncology, Henry Ford Hospital, Detroit, MI 48202.
S H
SH
Kim
J H
JH
Kim
G
G
Erdos
Y J
YJ
Lee
D000470:Alkaloids / Q000494:pharmacology*; D003110:Colonic Neoplasms; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D015870:Gene Expression / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D006358:Hot Temperature; D006801:Humans; D007700:Kinetics; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000302:isolation & purification; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism; D019311:Staurosporine; D014407:Tumor Cells, Cultured
D000470:Alkaloids; D006360:Heat-Shock Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D011493:Protein Kinase C; D019311:Staurosporine