Five cardiac hormones decrease the number of human small-cell lung cancer cells.
BACKGROUND
Four peptide hormones of a family of six hormones, i.e. atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), C-natriuretic peptide (CNP), long acting natriuretic peptide (LANP), vessel dilator and kaliuretic peptide, significantly decrease the number of adenocarcinoma cells in culture. The present investigation was designed to determine whether these peptide hormones' effects are specific to adenocarcinomas or whether they might decrease the number of cancer cells of a different type of cancer, i.e. small-cell lung cancer.


METHODS
These six hormones were evaluated for their ability to decrease the number and/or proliferation of human small-cell lung cancer cells in culture for 24, 48, 72, and 96 h.


RESULTS
Within 24 h, vessel dilator, LANP, kaliuretic peptide, ANP and their intracellular mediator cyclic GMP, each at 1 microM, decreased the number of small-cell lung cancer cells by 63% (P < 0.001), 21% (P < 0.05), 30% (P < 0.05), 39% (P < 0.05), and 31% (P < 0.05), respectively. There was no proliferation in the 3 days following this decrease in cell number. These same hormones decreased DNA synthesis 68% to 82% (P < 0.001). Brain natriuretic peptide and CNP did not decrease the number of small-cell lung cancer cells or inhibit their DNA synthesis at 1 microM or 10 microM concentrations. Dose-response curves revealed that at 100 microM, the vessel dilator decreased 92% of the cancer cells in 24 h while BNP had no effect, but CNP caused a 39% decrease. Western blots revealed that the natriuretic peptide receptors A- and C- were present in these cancer cells.


CONCLUSIONS
Five peptide hormones significantly decrease the number of human small-cell lung cancer cells within 24 h and inhibit their proliferation for at least 96 h. Their mechanism of doing so involves inhibition of DNA synthesis mediated in part by cyclic GMP.
Vesely
B A
BA
Department of Internal Medicine, University of South Florida Cardiac Hormone Center, Tampa, FL, USA.
Song
S
S
Sanchez-Ramos
J
J
Fitz
S R
SR
Alli
A A
AA
Solivan
S M
SM
Gower
W R
WR
Vesely
D L
DL
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009320:Atrial Natriuretic Factor / Q000032:analysis*; D015153:Blotting, Western; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D020097:Natriuretic Peptide, Brain / Q000494:pharmacology; D020098:Natriuretic Peptide, C-Type / Q000494:pharmacology; D011498:Protein Precursors / Q000494:pharmacology
D011498:Protein Precursors; D020097:Natriuretic Peptide, Brain; D020098:Natriuretic Peptide, C-Type; D009320:Atrial Natriuretic Factor