demecolcine and ethyl-2-5-dihydroxycinnamate

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.

Topics: Androstadienes; Breast; Cell Line; Cinnamates; Demecolcine; DNA; DNA Replication; Enzyme Inhibitors; Epidermal Growth Factor; Epithelium; ErbB Receptors; Estrenes; Female; Humans; Kinetics; Microtubules; Naphthalenes; Nitriles; Phosphorylation; Protein Kinase C; Pyrrolidinones; Type C Phospholipases; Tyrphostins; Wortmannin