Four cardiac hormones cause cell death of melanoma cells and inhibit their DNA synthesis.
BACKGROUND
There will be an estimated 59,940 new cases of melanoma and 8,110 deaths from melanoma in the United States in 2007. There has been no improvement in survival with melanomas in the last 22 years, with current treatment indicating that new treatment(s) of melanoma are drastically needed. Four cardiac hormones ie, atrial natriuretic peptide, vessel dilator, long-acting natriuretic peptide, and kaliuretic peptide, have significant anticancer effects in adenocarcinomas.


METHODS
Dose-response curves evaluated the effects of these cardiovascular hormones on cell death and DNA synthesis in several melanoma cell lines in culture for 96 hours. Receptors to mediate these peptide hormones effects were examined in the melanoma cells with Western blots. Their intracellular mediator-analog 8-bromo-cyclic GMP was used to determine if it could mimic their effects on decreasing melanoma cell number and DNA synthesis.


RESULTS
The four cardiac hormones caused cell death in up to 71% (P < 0.001) of the melanoma cells within 24 hours. Cardiac hormone receptors (NPR-A, -B, -C) were present on the melanoma cells, and each of the peptide hormones decreased DNA synthesis within the melanoma cells up to 73% (P < 0.001) at their 1-microM concentrations. 8-Bromo-cyclic GMP mimicked their effects, decreasing the number of melanoma cells up to 67% and their DNA synthesis by 58% (both at P < 0.01).


CONCLUSIONS
These results indicate that 4 cardiac hormones have potent beneficial effects by increasing cell death in up to 71% of melanoma cells within 24 hours mediated in part by a 73% decrease in their DNA synthesis.
Vesely
Brian A
BA
Departments of Internal Medicine, University of South Florida Cardiac Hormone Center, Tampa, Florida 33612, USA. david.vesely@med.va.gov
Eichelbaum
Ehrentraud J
EJ
Alli
Abdel A
AA
Sun
Ying
Y
Gower
William R
WR
Vesely
David L
DL
D000328:Adult; D009320:Atrial Natriuretic Factor / Q000235:genetics / Q000502:physiology*; D016923:Cell Death / Q000502:physiology; D045744:Cell Line, Tumor; D006152:Cyclic GMP / Q000494:pharmacology; D004273:DNA, Neoplasm / Q000378:metabolism*; D006162:Guanylate Cyclase / Q000378:metabolism; D006801:Humans; D008297:Male; D008545:Melanoma / Q000378:metabolism / Q000473:pathology*; D008875:Middle Aged; D010446:Peptide Fragments / Q000502:physiology; D011498:Protein Precursors / Q000502:physiology*; D017461:Receptors, Atrial Natriuretic Factor / Q000378:metabolism; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology*; D013997:Time Factors; D000099242:Atrial Natriuretic Factor Receptor B
D009320:Atrial Natriuretic Factor; D006152:Cyclic GMP; D004273:DNA, Neoplasm; D006162:Guanylate Cyclase; D010446:Peptide Fragments; D011498:Protein Precursors; D017461:Receptors, Atrial Natriuretic Factor; D000099242:Atrial Natriuretic Factor Receptor B; C075322:atrial natriuretic factor precursor (79-98); C054547:atrial natriuretic factor prohormone (1-30), human; C054548:atrial natriuretic factor prohormone (31-67); C091715:atrial natriuretic factor receptor A; C073616:atrial natriuretic factor receptor C