N‐terminal peptide fragments of lipocortin‐1 inhibit a549 cell growth and block EGF‐induced stimulation of proliferation

Abstract

Lipocortin-1 mediates growth inhibition of glucocorticoids in A549 cells by suppressing the release of PGE₂ necessary for their proliferation. We now show that 2 peptide fragments derived from the N-terminal portion of lipocortin-1 corresponding to amino-acids 13–25 and 21–33 also inhibited A549 cell growth and suppressed release of PGE₂, whereas peptides 1–12 and 13–25 (Phe²¹; in which the tyrosine at position 21 was replaced by a phenylalanine residue) were inactive. Similarly, peptide 21–33 (Phe²¹) and a scrambled sequence of 13–25 failed to inhibit cell growth. Moreover, the EGF-induced stimulation of cell proliferation 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 not by a scrambled sequence of peptide 13–25.