atrial-natriuretic-factor and Colonic-Neoplasms

β-Catenin causes malignant growth of colonic, pancreatic and renal cancer. Four cardiac hormones, namely atrial natriuretic peptide (ANP), vessel dilator, long-acting natriuretic peptide (LANP) and kaliuretic peptide eliminate up to 80% of human pancreatic carcinomas growing in mice.. Four cardiac hormones were evaluated for their ability to reduce the expression of human β-catenin, measured by enzyme-linked immunosorbent assay (ELISA) in human colorectal, pancreatic and renal cancer cells.. Vessel dilator, LANP, kaliuretic peptide, and ANP, over a concentration range of 100 pM to 10 μM, maximally reduced expression of β-catenin in human colorectal cancer cells by 78%, 71%, 69%, and 83%, respectively. Vessel dilator, LANP, kaliuretic peptide, and ANP reduced β-catenin expression in human pancreatic cancer cells by 76%, 66%, 72%, and 88%, and by 64%, 54%, 58% and 73%, in human renal cancer cells, respectively.. Part of the anticancer action of these four cardiac hormones is a potent inhibition of β-catenin.

Topics: Adenocarcinoma; Animals; Antineoplastic Agents; Atrial Natriuretic Factor; beta Catenin; Cell Line, Tumor; Colonic Neoplasms; Colorectal Neoplasms; Humans; Kidney Neoplasms; Mice; Pancreatic Neoplasms; Peptide Fragments; Protein Precursors

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.. 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.. 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.. 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.. Four peptide hormones eliminate up to 97% of colon cancer cells within 24 h with their DNA effects specifically mediated by cyclic GMP.

Topics: Adenocarcinoma; Atrial Natriuretic Factor; Cell Count; Cell Line, Tumor; Cell Proliferation; Cells, Cultured; Colonic Neoplasms; Cyclic GMP; DNA, Neoplasm; Dose-Response Relationship, Drug; Humans; Natriuretic Peptides; Peptide Fragments; Protein Precursors