N-TERMINAL PEPTIDE-FRAGMENTS OF LIPOCORTIN-1 INHIBIT A549 CELL-GROWTHAND BLOCK EGF-INDUCED STIMULATION OF PROLIFERATION

Lipocortin-I mediates growth inhibition of glucocorticoids in A549 cel ls by suppressing the release of PGE2 necessary for their proliferatio n. We now show that 2 peptide fragments derived from the N-terminal po rtion of lipocortin-I corresponding to amino-acids 13-25 and 21-33 als o inhibited A549 cell growth and suppressed release of PGE2, whereas p eptides 1-12 and 13-25 (Phe21; in which the tyrosine at position 21 wa s replaced by a phenylalanine residue) were inactive. Similarly, pepti de 21-33 (Phe21) and a scrambled sequence of 13-25 failed to inhibit c ell growth. Moreover, the EGF-induced stimulation of cell proliferatio n and PGE2 release in these cells was blocked by peptides 13-25 and 21 -33, and also by peptides 1-12, 13-25 (Phe21) and 21-33 (Phe21), but n ot by a scrambled sequence of peptide 13-25.