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Published on: May 14, 2016
Four peptides decrease human colon adenocarcinoma cell number and DNA synthesis via cyclic GMP
William R Gower1, Brian A Vesely, Abdel A Alli
1Department of Internal Medicine, University of South Florida Cardiac Hormone Center and James A. Haley Veterans Medical Center, Tampa, 33612, USA.
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.
Aim Of Study:
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.
Insights
Four peptide hormones significantly reduce colon cancer cells by up to 97% within 24 hours. These anticancer effects are mediated by cyclic guanosine monophosphate (cGMP).
Area of Science:
- Oncology
- Molecular Biology
- Endocrinology
Background:
- Colon cancer causes significant mortality, with limited treatment options.
- Natriuretic peptides demonstrate anticancer effects in other adenocarcinoma types.
Purpose of the Study:
- To investigate the anticancer effects of specific peptide hormones on colon adenocarcinoma cells.
- To determine if cyclic guanosine monophosphate (cGMP) mediates these anticancer effects.
Main Methods:
- Human colon adenocarcinoma cells were treated with four peptide hormones.
- Cell viability, proliferation, and DNA synthesis were assessed.
- The role of cGMP was evaluated using a cGMP antibody.
- Western blotting identified natriuretic peptide receptors (NPRs).
Main Results:
- A 89-97% decrease in colon cancer cells was observed within 24 hours.
- Concentration-dependent reduction in cell number and DNA synthesis (65-83%) occurred.
- cGMP mediated 75-97% of the observed anticancer and DNA synthesis effects.
- Natriuretic peptide receptors A and C were identified in colon cancer cells.
Conclusions:
- Four peptide hormones effectively eliminate a high percentage of colon cancer cells.
- The anticancer mechanisms are specifically mediated by cyclic guanosine monophosphate (cGMP).
- Natriuretic peptide receptors are present in colon adenocarcinoma cells, suggesting a potential therapeutic target.
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