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Four peptides decrease the number of human pancreatic adenocarcinoma cells
Author(s) -
Vesely B. A.,
McAfee Q.,
Gower W. R.,
Vesely D. L.
Publication year - 2003
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1046/j.1365-2362.2003.01262.x
Subject(s) - atrial natriuretic peptide , medicine , endocrinology , peptide hormone , natriuretic peptide , peptide , apoptosis , cell growth , hormone , pancreatic cancer , adenocarcinoma , cell culture , chemistry , npr1 , mechanism of action , biology , biochemistry , cancer , in vitro , heart failure , genetics
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 and materials These four peptide hormones, each at their 1‐µ m 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 E 2 , 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.