INHIBITION OF PROLIFERATION OF PRIMARY-CELL CULTURES AND OF L-132 CELLS BY PROTEIN-KINASE INHIBITORS

Background - We have previously shown that inhibition of protein kinas e C by 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H7), inhibits p roliferation of cells from neuroblastoma and other human brain tumors. We have now tested the effect of H7 on the proliferation of other cel l types. Moreover, we have examined the effect of other protein kinase inhibitors on the proliferation of L-132 cells. Methods - We have stu died the effect of H7 on DNA synthesis of primary cell cultures of fib roblasts, astrocytes and lymphocytes and the human fibroblast cell lin e L-132 and of N-(2-guanidinoethyl)-5-isoquinolinesulfonamide (HA 1004 ) and calphostin C on DNA synthesis and proliferation of L-132 cells. Results - H7 inhibited DNA synthesis to a different degree in all cell types tested. Moreover, H7, HA 1004 and calphostin C arrested prolife ration of L-132 cells. The antiproliferative effect induced by these c ompounds was reversible.Conclusions - These findings indicate that inh ibition of protein kinase C has an antiproliferative effect on differe nt cell types and that activation of both protein kinase C and cyclic nucleotide-dependent protein kinase is necessary for L-132 to continue to proliferate.