Inhibition of demecolcin-induced DNA synthesis by inhibitors of phospholipase C and protein kinase C.
Exposing normal human breast epithelia (HBE) cells, which were growth arrested by a 3-day culture in EGF-deprived medium, to the microtubule disrupting agent, demecolcin (N-deacetyl-N-methyl-colchicine), for 2 hr significantly stimulated the initiation of DNA synthesis 22 hr later. The demecolcin-induced DNA synthesis was not accompanied by activation of the EGF receptor and it was inhibited by calphostin C, an inhibitor of protein kinase C (PKC), and U-73122, an inhibitor of phospholipase C (PLC). Contrary to this, the EGF-induced DNA synthesis was inhibited by tyrphostin A25, a specific inhibitor of the EGF receptor tyrosine kinase, and calphostin C. The results suggested that the involvement of PLC and PKC in the demecolcin-induced signal transduction pathway leads to the initiation of DNA synthesis.
Suzuki
K
K
Department of Biochemistry, Kanagawa Cancer Center Research Institute, Japan.
Tsukatani
Y
Y
Takahashi
K
K
D000730:Androstadienes / Q000494:pharmacology; D001940:Breast; D002460:Cell Line; D002934:Cinnamates / Q000494:pharmacology; D004247:DNA / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D004261:DNA Replication / Q000187:drug effects*; D003703:Demecolcine / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004848:Epithelium; D066246:ErbB Receptors / Q000378:metabolism; D004963:Estrenes / Q000494:pharmacology; D005260:Female; D006801:Humans; D007700:Kinetics; D008870:Microtubules / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D009281:Naphthalenes / Q000494:pharmacology; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D011760:Pyrrolidinones / Q000494:pharmacology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors*; D020032:Tyrphostins; D000077191:Wortmannin
D000730:Androstadienes; D002934:Cinnamates; D004791:Enzyme Inhibitors; D004963:Estrenes; D009281:Naphthalenes; D009570:Nitriles; D011760:Pyrrolidinones; D020032:Tyrphostins; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; C079836:tyrphostin 25; C087931:ethyl 2,5-dihydroxycinnamate; D004815:Epidermal Growth Factor; D004247:DNA; D066246:ErbB Receptors; D011493:Protein Kinase C; D010738:Type C Phospholipases; C058819:calphostin C; D000077191:Wortmannin; D003703:Demecolcine