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Urodilatin and four cardiac hormones decrease human renal carcinoma cell numbers
Author(s) -
Vesely B. A.,
Eichelbaum E. J.,
Alli A. A.,
Sun Y.,
Gower W. R.,
Vesely D. L.
Publication year - 2006
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/j.1365-2362.2006.01721.x
Subject(s) - atrial natriuretic peptide , natriuretic peptide , medicine , endocrinology , brain natriuretic peptide , renal cell carcinoma , peptide hormone , npr2 , hormone , kidney , heart failure
Background Mortality from renal‐cell cancer remains a significant problem with an estimated 12 600 deaths in the United States in 2005 even with current treatment(s) of surgery, chemotherapy, radiation and immunotherapy. Four cardiac natriuretic peptides, that is, atrial natriuretic peptide, vessel dilator, long‐acting natriuretic peptide and kaliuretic peptide have significant anti‐cancer effects in breast, pancreatic, prostate and colon adenocarcinomas. Materials and methods These four peptide hormones plus brain natriuretic peptide (BNP), C‐natriuretic peptide (CNP) and urodilatin, a peptide hormone formed in the kidney by a different post‐translational processing of the atrial natriuretic peptide prohormone, were evaluated for their anti‐cancer effects in renal carcinomas. Results Dose–response curves revealed a significant ( P < 0·0001) decrease in human renal carcinoma cells with each 10‐fold increase in concentration from 1 µ m to 100 µ m of five of these peptide hormones. There was an 81%, 74%, 66%, 70% and 70% elimination within 24 h in renal carcinoma cells secondary to vessel dilator, kaliuretic peptide, urodilatin, atrial natriuretic peptide and long‐acting natriuretic peptide, respectively ( P < 0·0001 for each), whereas BNP had no effect and CNP decreased renal cancer cell number by 10% ( P = 0·04) at their 100 µ m concentrations. Three days after treatment with these peptide hormones, the cancer cells began to proliferate again. The four cardiac hormones and urodilatin decreased DNA synthesis from 65–84% ( P < 0·00001), whereas BNP and CNP decreased DNA synthesis 3% and 12% (both non‐significant). Western blots revealed for the first time natriuretic peptide receptors (NPR)‐A, ‐B and ‐C were present in the renal cancer cells. Conclusions These results indicate that urodilatin and the four cardiac hormones have potent anti‐cancer effects by eliminating up to 81% of renal carcinoma cells within 24 h of treatment.