Four peptides decrease the number of human pancreatic adenocarcinoma cells.
BACKGROUND
Long-acting natriuretic peptide, vessel dilator, kaliuretic peptide and atrial natriuretic peptide are four peptide hormones synthesized by the same gene. Their main known biologic properties are sodium and water excretion and blood pressure lowering in both animals and humans.


METHODS
These four peptide hormones, each at their 1-microm concentrations, were evaluated for their ability to decrease the number and/or proliferation of human pancreatic adenocarcinoma cells in culture at 24, 48, 72 and 96 h.


RESULTS
Vessel dilator, long-acting natriuretic peptide, kaliuretic peptide and atrial natriuretic peptide decreased the number of human pancreatic adenocarcinoma cells in culture by 65% (P<0.001), 47% (P<0.01), 37% (P<0.05) and 34% (P<0.05), respectively, within 24 h. This decrease was sustained without any proliferation of the cancer cells occurring in the 3 days following this decrease in number. The mechanism of these peptide hormones' decrease in cancer cell number and antiproliferative effects was a 83% (P<0.001) or greater inhibition of DNA synthesis but not owing to enhanced apoptosis, i.e. programmed cell death. The two known mediators of these peptide hormones' mechanism(s) of action, i.e. cyclic GMP and prostaglandin E2, inhibited DNA synthesis in these adenocarcinoma cells by 51% and 23%, respectively.


CONCLUSIONS
Four peptide hormones significantly decrease the number of pancreatic adenocarcinoma cells within 24 h and inhibit the proliferation of these cells for at least 96 h. Their mechanism of doing so is via inhibition of DNA synthesis mediated in part by cyclic GMP.
Vesely
B A
BA
Department of Medicine, University of South Florida Cardiac Hormone Center, Tampa, FL 33612, USA.
McAfee
Q
Q
Gower
W R
WR
Vesely
D L
DL
D000230:Adenocarcinoma / Q000473:pathology*; D017209:Apoptosis / Q000187:drug effects; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D006152:Cyclic GMP / Q000494:pharmacology; D004273:DNA, Neoplasm / Q000096:biosynthesis; D015232:Dinoprostone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D010190:Pancreatic Neoplasms / Q000473:pathology*; D010446:Peptide Fragments / Q000494:pharmacology; D011498:Protein Precursors / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D010446:Peptide Fragments; D011498:Protein Precursors; C075322:atrial natriuretic factor precursor (79-98); C054547:atrial natriuretic factor prohormone (1-30), human; C054548:atrial natriuretic factor prohormone (31-67); D009320:Atrial Natriuretic Factor; D006152:Cyclic GMP; D015232:Dinoprostone