atrial-natriuretic-factor and Carcinoma--Renal-Cell

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.. 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.. Dose-response curves revealed a significant (P < 0.0001) decrease in human renal carcinoma cells with each 10-fold increase in concentration from 1 microm to 100 microm 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 microm 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.. 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.

Topics: Aged; Antineoplastic Agents; Atrial Natriuretic Factor; Carcinoma, Renal Cell; Cell Proliferation; Humans; Kidney Neoplasms; Male; Natriuretic Peptide, Brain; Peptide Fragments; Receptors, Atrial Natriuretic Factor

The present studies were undertaken to assess the effects of atrial natriuretic factor (ANF) on erythropoietin (Ep) secretion in Ep-producing renal carcinoma (RC) cells using a sensitive radioimmunoassay for Ep. Human ANF produced a significant dose-related increase in Ep secretion at concentrations of 10(-7) and 10(-6) M when compared with vehicle controls. ANF (greater than or equal to 10(-9) M) also significantly increased the intracellular guanosine 3',5'-cyclic monophosphate (cGMP) concentration after 5-min incubation with the RC cells. Scatchard analysis of the human 125I-labeled ANF binding data indicated that the RC cells contain a single class of binding sites with a dissociation constant (Kd) of 93 +/- 1 pM and a binding capacity of 2,190 +/- 750 sites/cell. Incubation of the RC cells with 8-bromo-cGMP in concentrations of 10(-7)-10(-5) M also produced a significant dose-related enhancement of Ep secretion. These findings suggest that the increase in Ep secretion in response to ANF can be attributed, at least in part, to activation of guanylate cyclase, which is coupled to specific ANF receptors on the RC cell.

Topics: Atrial Natriuretic Factor; Carcinoma, Renal Cell; Cyclic GMP; Erythropoietin; Humans; Kidney Neoplasms; Kinetics; Lung Neoplasms; Tumor Cells, Cultured

Specific binding sites for atrial natriuretic peptide (99-126) in different areas of normal human renal tissue were quantified by in vitro autoradiography. Our data represent the first characterization of ANP binding sites in different structures of the human kidney. Characterization of ANP binding revealed by Scatchard plot analysis a single class of high affinity binding sites in the glomeruli (Kd 0.53 +/- 0.11 nM; BMax 74.4 +/- 17.86 fmol/mg protein), the vasculature (Kd 0.18 +/- 0.014 nM; BMax 91.6 +/- 25.02 fmol/mg protein), and the medulla (Kd 0.34 +/- 0.13 nM; BMax 106.0 +/- 30.61 fmol/mg protein). These sites may play a key role in the actions of the cardiac hormone in human kidney and in the ameliorating effects of ANP in the recovery from acute renal failure.

Topics: Aged; Aged, 80 and over; Atrial Natriuretic Factor; Autoradiography; Carcinoma, Renal Cell; Female; Humans; Kidney; Kidney Neoplasms; Male; Middle Aged; Receptors, Atrial Natriuretic Factor; Receptors, Cell Surface