Four peptides decrease human colon adenocarcinoma cell number and DNA synthesis via cyclic GMP.
BACKGROUND
Mortality from colon cancer is significant with an expected 30,350 colon cancer deaths in 2005 with current treatment(s). Long-acting natriuretic peptide, vessel dilator, kaliuretic peptide, and atrial natriuretic peptide have significant anticancer effects in breast and pancreatic adenocarcinomas.


OBJECTIVE
Whether these peptide hormones have anticancer effects in colon adenocarcinoma cells and whether these effects are specifically mediated by cyclic GMP has not been determined.


METHODS
These peptide hormones were evaluated for anticancer effects in human colon adenocarcinoma cells and to determine whether their anticancer effects are specifically mediated by cyclic GMP.


RESULTS
There was a 89-97% decrease (p <0.001 for each) in colon adenocarcinoma cells within 24 h with 1 mM of these peptide hormones. There was a significant (p <0.05) decrease in human colon cancer cell number with each 10-fold increase in concentration from 1 to 1,000 microM (i.e., 1 mM) of these four peptide hormones without any proliferation in the 3 d following this decrease. These same hormones decreased DNA synthesis 65-83% (p <0.001). Cyclic GMP antibody inhibited 75- 80% of these peptides' ability to decrease colon adenocarcinoma cell number and inhibited 92-96% of their DNA synthesis effects and 97% of cyclic GMP's effects. Western blots revealed that for the first time natriuretic peptide receptors (NPR) A and C were present in colon adenocarcinoma cells.


CONCLUSIONS
Four peptide hormones eliminate up to 97% of colon cancer cells within 24 h with their DNA effects specifically mediated by cyclic GMP.
Gower
William R
WR
Department of Internal Medicine, University of South Florida Cardiac Hormone Center and James A. Haley Veterans Medical Center, Tampa, 33612, USA.
Vesely
Brian A
BA
Alli
Abdel A
AA
Vesely
David L
DL
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D002452:Cell Count; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006152:Cyclic GMP / Q000494:pharmacology; D004273:DNA, Neoplasm / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D006801:Humans; D045265:Natriuretic Peptides / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology; D011498:Protein Precursors / Q000494:pharmacology*
D004273:DNA, Neoplasm; D045265:Natriuretic Peptides; D010446:Peptide Fragments; D011498:Protein Precursors; C075322:atrial natriuretic factor precursor (79-98); C054548:atrial natriuretic factor prohormone (31-67); D009320:Atrial Natriuretic Factor; D006152:Cyclic GMP