Selective inhibition of the growth of ras-transformed human bronchial epithelial cells by emodin, a protein-tyrosine kinase inhibitor.
Emodin (3-methyl-1,6,8-trihydroxyanthraquinone), a naturally occurring protein-tyrosine kinase inhibitor, selectively blocked the growth of v-ras-transformed human bronchial epithelial cells. Half-maximal inhibition of cell growth occurred at a concentration of 4 micrograms/ml. In contrast, emodin at a concentration of 100 micrograms/ml had little effect on the growth of normal human bronchial epithelial cells. Cell cycle analyses indicated that treatment with emodin arrested the v-ras-transformed cells in the G2/M phase of their cell cycle. Immunoblotting experiments using anti-phosphotyrosine antibodies indicated that ras-transformed cells, as compared to their normal counterparts, exhibited elevated levels of phosphotyrosine-containing proteins. Treatment with emodin resulted in a decrease in intracellular protein-tyrosine phosphorylation. These results suggest that compounds that inhibit the ras-dependent elevation in the level of tyrosine phosphorylated proteins may prove to be useful chemotherapeutic agents and may exhibit selective cytotoxicity against cancer cells with an activated ras oncogene.
Chan
T C
TC
Department of Veterinary Physiology and Pharmacology, Purdue University, West Lafayette, IN 47907.
Chang
C J
CJ
Koonchanok
N M
NM
Geahlen
R L
RL
D001980:Bronchi; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000633:toxicity; D004642:Emodin / Q000494:pharmacology* / Q000633:toxicity; D004848:Epithelium; D011905:Genes, ras; D006801:Humans; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis
D019000:Phosphotyrosine; D014443:Tyrosine; D004317:Doxorubicin; D011505:Protein-Tyrosine Kinases; D004642:Emodin