Inhibitory action of epiderstatin on EGF-stimulated growth of mouse epidermal. BALB/MK cells without direct effect on protein kinase activities.
Epiderstatin, a distinctive glutarimide antibiotic isolated from Streptomyces pulveraceus subsp. epiderstagenes, has been revealed to be a potent inhibitor of the signal transduction of epidermal growth factor (EGF). Epiderstatin inhibited the DNA synthesis induced by various peptide growth factors in a mouse epidermal cell line, BALB/MK, without inhibiting protein tyrosine kinase activity of EGF-receptor or serine/threonine kinase activity of protein kinase C. The 50% inhibitory concentration (IC50) value of epiderstatin for the EGF-stimulated incorporation of [3H]thymidine into BALB/MK cells was about 10 nM. When epiderstatin was added to the quiescent cells simultaneously with EGF-stimulation, the cells did not reenter into the growing cell cycle. The action of epiderstatin proceeded from the overexpression of c-fos and the suppression of c-myc transcription when EGF was added to quiescent BALB/MK cells.
Osada
H
H
Institute of Physical and Chemical Research (RIKEN), Saitama, Japan.
Kikuchi
K
K
Makishima
F
F
Isono
K
K
D000199:Actins / Q000235:genetics; D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002472:Cell Transformation, Viral; D004247:DNA / Q000096:biosynthesis; D000078404:Epidermal Cells; D004815:Epidermal Growth Factor / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism; D066246:ErbB Receptors / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D016762:Genes, fos; D016259:Genes, myc; D015603:Keratinocytes / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010881:Piperidones / Q000494:pharmacology*; D011494:Protein Kinases / Q000187:drug effects* / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000187:drug effects / Q000378:metabolism; D011728:Pyridones / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D013268:Stimulation, Chemical; D014158:Transcription, Genetic / Q000187:drug effects
D000199:Actins; D010881:Piperidones; D011728:Pyridones; C061874:epiderstatin; D004815:Epidermal Growth Factor; D004247:DNA; D011494:Protein Kinases; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases