N-terminal peptide fragments of lipocortin-1 inhibit A549 cell growth and block EGF-induced stimulation of proliferation.
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.
Croxtall
J D
JD
Department of Biochemical Pharmacology, William Harvey Research Institute, Medical College, St. Batholomew's Hospital, London, UK.
Waheed
S
S
Choudhury
Q
Q
Anand
R
R
Flower
R J
RJ
D000230:Adenocarcinoma / Q000473:pathology*; D000595:Amino Acid Sequence; D017305:Annexin A1 / Q000737:chemistry / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D015232:Dinoprostone / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000037:antagonists & inhibitors*; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D017305:Annexin A1; D010446:Peptide Fragments; D004815:Epidermal Growth Factor; D015232:Dinoprostone