EFFECT OF PROTEIN-KINASE-C INHIBITORS ON TPA-INDUCED INHIBITION OF GAP JUNCTIONAL INTERCELLULAR COMMUNICATION AND INDUCTION OF TRANSFORMED MORPHOLOGY IN SYRIAN-HAMSTER EMBRYO CELLS
Le. Roseng et al., EFFECT OF PROTEIN-KINASE-C INHIBITORS ON TPA-INDUCED INHIBITION OF GAP JUNCTIONAL INTERCELLULAR COMMUNICATION AND INDUCTION OF TRANSFORMED MORPHOLOGY IN SYRIAN-HAMSTER EMBRYO CELLS, Toxicology in vitro, 7(5), 1993, pp. 637-644
Staurosporine and H-7, but not polymyxin B, were found partly to suppr
ess the effect of TPA on both inhibition of gap junctional intercellul
ar communication (GJIC), down-regulation of EGF-binding and induction
of transformed morphology in Syrian hamster embryo (SHE) cells. The pa
rallel effect of these kinase inhibitors suggests that TPA induces the
effects through activation of protein kinase C (PKC). This is consist
ent with the view that PKC is involved in both the induction of transf
ormed morphology and the inhibition of GJIC. All the inhibitors studie
d reduced PKC activity in SHE cell extracts. IC50 values were determin
ed to be 0.008 mu M for staurosporine, 55 mu M for H-7 and 16 mu M for
polymyxin B. The values for staurosporine and H-7 corresponded to tho
se concentrations that suppressed TPA-induced cellular responses. The
lack of effect of polymyxin B on whole SHE cells indicates that this c
ompound does not enter the cells.