Long-acting Natriuretic Peptide Research Articles

Phase 1 safety, tolerability, pharmacokinetics and pharmacodynamics results of a long-acting C-type natriuretic peptide prodrug, TransCon CNP

Phase 1 safety, tolerability, pharmacokinetics and pharmacodynamics results of a long-acting C-type natriuretic peptide prodrug, TransCon CNP

Sustained Activation of Guanylate Cyclase-A with TDT, a Natriuretic Peptide Derivative, Exhibits Cardiorenal Protection in Dahl Salt-Sensitive Hypertensive Rats.

Heart failure often presents with prognosis-relevant impaired renal function. To investigate whether the chronic activation of guanylate cyclase-A (GC-A) protects both heart and kidney, we examined the effects of TDT, a neprilysin (NEP)-resistant natriuretic peptide (NP) derivative, on cardiac and renal dysfunction in Dahl salt-sensitive hypertensive (DS) rats. Pretreatment with NEP or NEP inhibitor did not influence GC-A activation by TDT both in vitro and in vivo, resulting in a long-acting profile of TDT compared with native human atrial NP (hANP). The repeated administration of TDT to DS rats suppressed the progress of cardiac hypertrophy, systolic/diastolic dysfunction, and proteinuria in a dose-dependent manner. Compared with vehicle and hANP, salt diet-induced podocyte injury was reduced by TDT, as analyzed by urinary podocalyxin concentration, renal expression of nephrin mRNA, and glomerular expression of desmin protein. Since glomerular TRPC6 plays detrimental roles in podocyte homeostasis, we examined the renal expression of TRPC6 in DS rats and found that salt diet upregulated the expression of TRPC6. Importantly, TRPC6 induction was significantly decreased in TDT-treated rats, compared with vehicle and hANP. Consistently, in primary-culture podocytes from DS rats, TDT inhibited ATP-induced calcium influx, similar to TRPC inhibitor SKF96365. Finally, TDT-mediated protection of podocytes was abolished by protein kinase G inhibitor KT5823. In conclusion, TDT treatment attenuated heart and kidney dysfunction, accompanied by podocyte protection through inhibition of TRPC6. Thus, long-acting NPs could be a new avenue for treatment of heart failure.

Heart Peptide Hormones: Adjunct and Primary Treatments of Cancer.

These multiple kinase inhibitors have both adjunct and primary anticancer effects.

Cardiac hormones target nuclear oncogenes c‐Fos and c‐Jun in carcinoma cells

c-Fos is a cellular proto-oncogene which dimerizes with c-Jun proto-oncogene to form AP-1 transcription factor, which upregulates transcription of genes involved in proliferation and cancer formation. Four cardiac hormones, that is, long-acting natriuretic peptide (LANP), vessel dilator, kaliuretic peptide (KP) and atrial natriuretic peptide (ANP) with anticancer effects in vivo are potent inhibitors of the Ras-MEK 1/2-ERK 1/2 kinase cascade and signal transducer and activator of transcription-3 (STAT-3) that activate c-Fos and c-Jun. These four cardiac hormones were investigated for their effects on proto-oncogenes c-Fos and c-Jun within the nucleus of cancer cells. Four cardiac hormones were evaluated for their ability to decrease proto-oncogenes c-Fos and c-Jun, measured by ELISA in extracted nuclei of three human cancer cell lines. Vessel dilator, LANP, KP and ANP over a concentration range of 100 pM-10 μM, maximally decreased c-Fos by 61%, 60%, 61% and 59% in human hepatocellular cancer cells, by 82%, 74%, 78% and 74% in small-cell lung cancer cells, and by 82%, 73%, 78% and 74% in human renal adenocarcinoma cells. c-Jun was maximally reduced by vessel dilator, LANP, KP and ANP by 43%, 31%, 61% and 35% in hepatocellular cancer cells, by 65%, 49%, 59% and 40% in small-cell lung cancer cells, and by 47%, 43%, 57% and 49% in renal cancer cells. Four cardiac hormones are potent inhibitors of c-Fos and c-Jun proto-oncogenes within the nucleus of cancer cells.

Fasting Serum Long-Acting Natriuretic Peptide Correlates With the Ankle Brachial Index in Renal Transplant Recipients

Peripheral arterial diseases associated with an increased risk of death in kidney transplant patients. Natriuretic peptide has anti-atherosclerotic effects. We sought to evaluate the relation between ankle-brachial index and fasting serum long-acting natriuretic peptide concentrations in kidney transplant patients. Fasting blood samples were obtained from 69 kidney transplant patients. Serum long-acting natriuretic peptide concentrations were measured using a commercially available enzyme immunoassay kit. Left or right ankle-brachial index values that were < 0.9 were included in the low ankle-brachial index group. Fifteen patients (21.7%) were enrolled in the low ankle-brachial index group. Increased waist circumference (P = .013), higher serum total cholesterol levels (P = .019), higher triglyceride levels (P = .002), and decreased serum long-acting natriuretic peptide concentrations (P = .006) were noted in the low ankle-brachial index group. Univariate linear regression analysis indicated that the left/right ankle-brachial index values of the subjects were negatively correlated with serum triglycerides (P = .008 or P < .001) and fasting glucose levels (P = .034 or P = .012), but were positively correlated with long-acting natriuretic peptide concentrations (P = .011 or P = .011). Multivariate forward stepwise linear regression analyses of the significant variables revealed that serum triglycerides and long-acting natriuretic peptide levels were independent predictors of the left/right ankle-brachial index values of kidney transplant patients. Serum long-acting natriuretic peptide concentrations correlate positively with ankle-brachial index values among the kidney transplant patients.

Reduction of leptin levels by four cardiac hormones: Implications for hypertension in obesity

Circulating levels of leptin are increased in obesity and have been proposed to contribute to the development of hypertension in obese individuals. Four cardiac hormones, specifically, vessel dilator, long-acting natriuretic peptide (LANP), kaliuretic peptide and atrial natriuretic peptide (ANP), have blood pressure-lowering properties and correlate with the presence of hypertension in obesity. The objective of this study was to determine whether one or more of these cardiac hormones was able to decrease the levels of leptin in the hypothalamus, an area of the brain that has been demonstrated to synthesize more than 40% of leptin in the circulation. The effects of these four cardiac hormones on leptin were examined using dose-response curves in the rat hypothalamus, which synthesizes leptin. Vessel dilator, LANP, kaliuretic peptide and ANP maximally decreased the levels of leptin in hypothalamic cells by 79, 76, 80 and 62%, respectively (P<0.0001 for each). The cardiac hormones decreased leptin levels over a concentration range of 100 pM to 10 μM, with the most significant reductions in leptin levels occurring when the concentrations of the hormones were at micromolar levels. The results of the study suggest that the four cardiac hormones lead to significant reductions in hypothalamic leptin levels, which may be an important mechanism for alleviating leptin-induced hypertension in obesity.

Inverse association of long-acting natriuretic peptide with metabolic syndrome in congestive heart failure patients

AimsLong-acting natriuretic peptide (LANP) is one of the peptide hormones in atrial natriuretic peptide (ANP) pro-hormone. Low levels of natriuretic peptide may lead to reduced lipolysis and excessive weight gain in obese patients. The aim of this study was to investigate the relationship between fasting serum LANP level and the metabolic syndrome (MetS) among congestive heart failure (CHF) patients.MethodsFasting blood samples were obtained from 186 patients with normal renal function in cardiac clinic outpatients. CHF defined by the American College of Cardiology Foundation and the American Heart Association 2005 Guidelines. MetS and its components were defined using diagnostic criteria from the International Diabetes Federation.ResultsNinety-eight patients (52.7%) had CHF. There was a tendency of increased fasting LANP levels as the NYHA CHF functional classes increased (p = 0.002). Forty-six of the CHF patients (46.9%) had MetS. Fasting LANP level negatively correlated with MetS among CHF patients (p < 0.001). Univariate linear regression analysis showed that BUN (p = 0.026) positively correlated with fasting serum LANP levels, while body weight (p = 0.009), BMI (p = 0.004), homeostasis model assessment of insulin resistance (HOMA-IR; p = 0.024) and HOMA-β (p = 0.001) negatively correlated with fasting serum LANP levels among the CHF patients. Multivariate forward stepwise linear regression analysis of the significant variables showed that the HOMA-β (R2 change = 0.292, p < 0.001) and HOMA-IR (R2 change = 0.081, p = 0.019) were independent predictors of fasting serum LANP levels in CHF patients.ConclusionsLANP level is significantly reduced in CHF patients affected by MetS. HOMA-β and HOMA-IR were independent predictors of serum LANP levels in CHF patients.

Cardiac hormones for the treatment of cancer

Four cardiac hormones, namely atrial natriuretic peptide, vessel dilator, kaliuretic peptide, and long-acting natriuretic peptide, reduce up to 97% of all cancer cells in vitro. These four cardiac hormones eliminate up to 86% of human small-cell lung carcinomas, two-thirds of human breast cancers, and up to 80% of human pancreatic adenocarcinomas growing in athymic mice. Their anticancer mechanisms of action, after binding to specific receptors on cancer cells, include targeting the rat sarcoma-bound GTP (RAS) (95% inhibition)-mitogen-activated protein kinase kinase 1/2 (MEK 1/2) (98% inhibition)-extracellular signal-related kinase 1/2 (ERK 1/2) (96% inhibition) cascade in cancer cells. They also inhibit MAPK9, i.e. c-Jun N-terminal kinase 2. They are dual inhibitors of vascular endothelial growth factor (VEGF) and its VEGFR2 receptor (up to 89%). One of the downstream targets of VEGF is β-catenin, which they reduce up to 88%. The WNT pathway is inhibited up to 68% and secreted frizzled-related protein 3 decreased up to 84% by the four cardiac hormones. AKT, a serine/threonine protein kinase, is reduced up to 64% by the cardiac hormones. STAT3, a final 'switch' that activates gene expression that leads to malignancy, is decreased by up to 88% by the cardiac hormones. STAT3 is specifically decreased as they do not affect STAT1. There is a cross-talk between the RAS-MEK 1/2-ERK 1/2 kinase cascade, VEGF, β-catenin, WNT, JNK, and STAT pathways and each of these pathways is inhibited by the cardiac hormones.

Low Serum Long-acting Natriuretic Peptide Level Correlates with Metabolic Syndrome in Hypertensive Patients: A Cross-sectional Study

Long-acting natriuretic peptide (LANP) is one of the peptide hormones in atrial natriuretic peptide (ANP) prohormone. Its biological properties are blood pressure regulation, maintenance of plasma volume and anticancer effects. The aim of this study was to evaluate the relationship between metabolic syndrome (MetS) and fasting serum LANP concentration in hypertensive patients. Fasting blood samples were obtained from 224 patients with or without hypertension. MetS and its components were defined using diagnostic criteria from the International Diabetes Federation. Eighty-eight hypertensive patients (59.5 %) had MetS. Hypertensive patients with MetS had higher body weight (p= 0.003), waist circumference (p= 0.003), body mass index (p= 0.002), triglyceride concentrations (p= 0.029), insulin levels (p= 0.001), HOMA-IR (p <0.003) and HOMA-β (p= 0.049) and lower HDL-C concentrations (p= 0.001), LANP levels (p= 0.012) than those without MetS. The univariable linear regression analysis showed that age (p= 0.038) and the BUN concentration (p= 0.022) were positively correlated with the serum LANP levels, whereas the insulin level (p= 0.001), HOMA-IR (p= 0.004), and HOMA-β (p= 0.001) were negatively correlated with the fasting serum LANP levels among the hypertensive patients. Multivariable forward stepwise linear regression analysis of the significant variables showed that the HOMA-β (β= -0.387, R(2)= 0.141, p <0.001) was an independent predictor of fasting serum LANP levels in hypertensive patients. LANP level is significantly reduced in hypertensive patients affected by MetS and is negatively related to pancreatic beta cell function in hypertensive patients.

Fasting Serum Long-Acting Natriuretic Peptide Correlates with the Ankle Brachial Index of Renal Transplant Recipients

Fasting Serum Long-Acting Natriuretic Peptide Correlates with the Ankle Brachial Index of Renal Transplant Recipients

Potent selective inhibition of STAT 3 versus STAT 1 by cardiac hormones

Signal transducers and activators of transcription (STATs) are the final "switches" that activate gene expression patterns that lead to human malignancy. Extracellular signal-regulated kinases (ERK 1/2) activate STAT 3; four cardiovascular hormones inhibit ERK 1/2 kinases, leading to the hypothesis that they may also inhibit STATs. These four cardiac hormones, i.e., vessel dilator, long-acting natriuretic peptide (LANP), kaliuretic peptide, and atrial natriuretic peptide (ANP), eliminate human cancers growing in mice. These four cardiac hormones' effects on STATs 1 and 3 were examined in human small-cell lung cancer and human pancreatic adenocarcinoma cells. Vessel dilator, LANP, kaliuretic peptide, and ANP maximally decreased STAT 3 by 88, 54, 55, and 65 %, respectively, at their 1 μM concentrations in human small-cell lung cancer cells and STAT 3 by 66, 57, 70, and 77 % in human pancreatic adenocarcinoma cells, respectively. The cardiac hormones (except LANP) also significantly decreased STAT 3 measured by Western blots. These cardiac hormones did not decrease STAT 1 in either human small-cell lung cancer or pancreatic adenocarcinoma cells. We conclude that these four cardiac hormones are significant inhibitors of STAT 3, but not STAT 1, in human small-cell lung cancer and pancreatic adenocarcinoma cells, which suggests a specificity for these hormones' anticancer mechanism(s) of action enzymology in human cancer cells.

Novel dual inhibitors of vascular endothelial growth factor and VEGFR2 receptor

Vascular endothelial growth factor (VEGF) helps control tumour growth via causing new capillaries growth in tumours. Four cardiac hormones [i.e. vessel dilator, long-acting natriuretic peptide (LANP), kaliuretic peptide (KP) and atrial natriuretic peptide (ANP)] that eliminate up to up to 86% of human small-cell lung cancers growing in mice were investigated for their effects on VEGF and the VEGFR2/KDR/Flk-1 receptor. The VEGFR2 receptor is the main receptor mediating VEGF's cancer-enhancing effects. Four cardiac hormones were evaluated for their ability to decrease VEGF/VEGFR2 measured by ELISAs in three human cancer cell lines. Vessel dilator, LANP, KP and ANP, over a concentration range of 100 pM to 10 μM, maximally decreased the VEGFR2 receptor in human pancreatic adenocarcinoma cells by 48%, 49%, 74% and 83%. Vessel dilator, LANP, KP and ANP decreased the VEGFR2 receptor by 77%, 89%, 88% and 67% in human small-cell lung cancer cells and by 48%, 92%, 64% and 71% in human prostate cancer cells. These results were confirmed with the cardiac hormones also decreasing the VEGFR2 receptor measured by Western blots. VEGF itself in pancreatic carcinoma cells was decreased by 42%, 58%, 36% and 40% by vessel dilator, LANP, KP and ANP. VEGF levels were decreased 25%, 23%, 17% and 23% in small-cell lung cancer cells and decreased by 24%, 20%, 23% and 24% in prostate cancer cells by vessel dilator, LANP, KP and ANP. Four cardiac hormones are the first dual inhibitors of VEGF and the VEGFR2/KDR/Flk-1 receptor.

Fasting Long-Acting Natriuretic Peptide Correlates Inversely With Metabolic Syndrome in Kidney Transplant Patients

The metabolic syndrome (MetS) is a risk factor for posttransplant diabetes mellitus, chronic graft dysfunction, graft loss, occurrence of atherosclerotic events, and patient death among kidney transplantation patients. Long-acting natriuretic peptide (LANP) is among the peptide hormones in atrial natriuretic peptide prohormone. Low levels of natriuretic peptide may lead to reduced lipolysis and excessive weight gain in obese patients. This study was undertaken to evaluate the relationship between MetS and fasting serum LANP concentration among kidney transplanted patients. Fasting blood samples were obtained from 69 kidney recipients. The MetS and its components were defined using the diagnostic criteria of the International Diabetes Federation. Fasting LANP levels were measured using a commercial enzyme immunoassay kit. The prevalence rate of MetS was 20.3% (14/69). Fasting LANP level negatively correlated with MetS among these patients (P = .010). Using univariate linear regression analysis, serum LANP values were negatively correlated with hemoglobin (r = −0.252; P = .037), and positively correlated with blood urea nitrogen (r = 0.254; P = .035) and creatinine (r = 0.311; P = .009). Multivariate forward stepwise linear regression analysis of the significant variables revealed that creatinine (R2 change = 0.097; P = .009) was an independent predictor of fasting serum LANP concentration among kidney transplanted patients. Serum LANP concentration correlates inversely with MetS; for these patients, creatinine is an independent predictor of the serum LANP value.

563 Measurement of Long-acting Natriuretic Peptide (Lanp) in Exacerbation of Asthma

BackgroundEvidence exists that atrial natriuretic peptide (ANP) is a regulator of smooth muscle airway tone and is a potent bronchodilator and immune modulator in animals. Objective: Long-acting natriuretic peptide (LANP), encoded by the same gene and derived from the same pro-hormone as ANP, was measured in patients with acute asthma exacerbation pre- and post-treatment with systemic or inhaled glucocorticosteroids.MethodsMeasurement of LANP was obtained from plasma samples in 15 subjects with acute asthma exacerbation, by an enzyme immunoassay technique. A repeat measurement of LANP was obtained 5 to 7 and 10 to 14 days after initiation of treatment.ResultsNo significant differences were found compared to baseline in plasma LANP level after treatment of the asthma exacerbation (P = 0.8904). The average LANP values were 2.12 higher in the oral glucocorticosteroid group versus the inhaled glucocorticosteroid group, (P = 0.0608). There was no significant difference in LANP levels between male and females (P = 0.5743), with antibiotic use (P = 0.9437), or with age (P = 0.6384).ConclusionsPlasma LANP level did not differ before and after treatment for an asthma exacerbation. Measuring plasma LANP pro-hormone was not helpful in assessing treatment outcome of asthma exacerbation.

Inverse association of serum long-acting natriuretic peptide and bone mineral density in renal transplant recipients

Our aim was to evaluate the relationship between bone mineral density (BMD) and fasting serum long-acting natriuretic peptide (LANP) concentration in renal transplant recipients. Fasting blood samples were obtained from 65 renal transplant recipients. BMD was measured using dual energy X-ray absorptiometry in lumbar vertebrae (L2-L4). Serum LANP levels were measured using a commercial enzyme immunoassay kit. Six patients (9.2%) had osteoporosis and 28 patients (43.1%) had osteopenia in renal transplant recipients. Increased serum LANP (p<0.001) was significantly correlated with low lumbar T-score cut-off points between groups (normal, osteopenia, and osteoporosis) in renal transplant recipients. Female patients had lower lumbar BMD than male renal transplant recipients (p=0.027). Univariate linear regression analysis indicated that lumbar BMD were positively correlated with height (p=0.038), body weight (p=0.003), and body mass index (BMI; p=0.019), whereas negatively correlated with LANP (p=0.004) among the renal transplant recipients. Multivariate forward stepwise linear regression analysis of the significant variables revealed that body weight (R(2) change=0.132; p=0.006) and LANP (R(2) change=0.093; p=0.008) were the independent predictors of lumbar BMD values in the renal transplant recipients. Serum LANP concentration correlates negatively with lumbar BMD values in renal transplant recipients.

Cardiac Hormones Target the Ras-MEK 1/2-ERK 1/2 Kinase Cancer Signaling Pathways

The heart is a sophisticated endocrine gland synthesizing the atrial natriuretic peptide prohormone which contains four peptide hormones, i.e., atrial natriuretic peptide, vessel dilator, kaliuretic peptide and long-acting natriuretic peptide, which decrease up to 97% of human pancreatic, breast, colon, prostate, kidney and ovarian carcinomas as well as small-cell and squamous cell lung cancer cells in cell culture. In vivo, these four cardiac hormones eliminate up to 80% of human pancreatic adenocarcinomas, two-thirds of human breast cancers, and up to 86% of human small-cell lung cancers growing in athymic mice. Their signaling in cancer cells includes inhibition of up to 95% of the basal activity of Ras, 98% inhibition of the phosphorylation of the MEK 1/2 kinases and 97% inhibition of the activation of basal activity of the ERK 1/2 kinases mediated via the intracellular messenger cyclic GMP. They also completely block the activity of mitogens such as epidermal growth factor's ability to stimulate ERK and Ras. They do not inhibit the activity of ERK in healthy cells such as human fibroblasts. The final step in their anticancer mechanism of action is that they enter the nucleus as demonstrated by immunocytochemical studies to inhibit DNA synthesis within cancer cells.

Cardiac hormones inhibit proliferation of pancreatic cancer but not normal cells

Four cardiac hormones, i.e. atrial natriuretic peptide (ANP), vessel dilator, long-acting natriuretic peptide (LANP) and kaliuretic peptide (KP), have anticancer effects both in vitro and in vivo. The sustained decrease in number of human pancreatic adenocarcinoma cells for 3 days secondary to the four hormones noted previously suggests a decrease in proliferation of pancreatic cancer cells not eliminated after initial treatment. Four cardiac hormones were evaluated for their ability to directly decrease proliferation of human pancreatic cancer cells with comparison of their effects on proliferation on normal human lung, kidney, prostate and endothelial cells. ANP, LANP, vessel dilator and KP decreased the proliferation of viable human pancreatic adenocarcinoma cells by 39%, 73%, 26% and 32% respectively at their 0.01 microM concentrations compared with the proliferation of untreated pancreatic cancer cells. Maximal inhibition of proliferation (81%) occurred with LANP at its 0.1 microM concentration in dose-response studies. At these same concentrations, there was no decrease in proliferation of human kidney, lung, prostate or endothelial cells compared with untreated kidney, lung, prostate or endothelial cells. Four cardiac hormones have strong anti-proliferative effects on human pancreatic adenocarcinoma cells while sparing human kidney, lung, prostate and endothelial cells from a similar strong anti-proliferative effect. This anti-proliferative effect on pancreatic cancer cells helps to explain why human pancreatic cancers in vivo treated with the cardiac hormones decrease to less than 10% of the volume of untreated pancreatic cancers as they proliferate less.

Epidermal growth factor’s activation of Ras is inhibited by four cardiac hormones

Four cardiac hormones synthesized by the same gene, i.e. atrial natriuretic peptide, vessel dilator, kaliuretic peptide and long-acting natriuretic peptide, have anticancer effects in vitro and in vivo. Epidermal growth factor's mechanism of cancer formation involves the activation of Ras. These four cardiac hormones were evaluated for their ability to inhibit mitogen (epidermal growth factor) activation of Ras. Epidermal growth factor increased the activation of Ras by 68%, 85% and 90% at its 1, 2 and 5 ng mL(-1) concentrations. Vessel dilator, long-acting natriuretic peptide, atrial natriuretic peptide and kaliuretic peptide inhibited 5 ng mL(-1) epidermal growth factor's stimulation of Ras by 73%, 79%, 33% and 45%, respectively, at their 1 microM concentrations. Their effects on epidermal growth factor's activation of Ras were specific with addition of the cardiac hormones' respective antibodies (5 microM) blocking 95%, 93%, 100% and 100% (P < 0.001 for each) of their ability to inhibit epidermal growth factor's stimulation of Ras. Four cardiac hormones specifically inhibit epidermal growth factor's activation of Ras. This investigation would suggest that these cardiac hormones' anticancer effects involve the inhibition of mitogens such as epidermal growth factor's ability to activate Ras as well as inhibiting unstimulated basal activity of Ras.

Metabolic Targets of Cardiac HormonesTherapeutic Anti-Cancer Effects

The heart is a sophisticated endocrine gland synthesizing a family of peptide hormones by three different genes. These cardiac hormones are stored as 3 prohormones, i.e. atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) prohormones. Within the ANP prohormones are 4 peptide hormones, i.e. atrial natriuretic peptide, vessel dilator, kaliuretic peptide and long-acting natriuretic peptide (LANP) which decrease up to 97% of human pancreatic, breast, colon, prostate, kidney and ovarian carcinomas as well as small-cell and squamous cell lung cancer cells within 24 hours in cell culture. In vivo these 4 cardiac hormones eliminate up to 80% of human pancreatic adenocarcinomas, 2/3rds of human breast cancers, and up to 86% of human small-cell lung cancers in athymic mice. Their anticancer mechanism(s) target the Ras-MEK 1/2-ERK 1/2 kinase cascade in cancer cells. These 4 cardiac hormones inhibit up to 95% of the basal activity of Ras, 98% of the phosphorylation of MEK 1/2 and 97% of the activation of basal activity of ERK 1/2. They also completely block the activity of mitogens such as epidermal growth factor's ability to stimulate ERK. They do not inhibit the activity of ERK in healthy cells such as human fibroblasts. The final step in their anticancer mechanism of action is that they enter the nucleus as demonstrated by immunfluorescence to inhibit DNA synthesis within cancer cells.

Cardiac hormones eliminate some human squamous lung carcinomas in athymic mice

Four cardiac hormones synthesized by the same gene, i.e. atrial natriuretic peptide, vessel dilator, long acting natriuretic peptide and kaliuretic peptide, have anticancer effects in vitro. These cardiac hormones were infused subcutaneously for 28 days with weekly fresh hormones at 0.3 nM kg(-1) body weight in athymic mice bearing human squamous cell carcinomas. Vessel dilator, atrial natriuretic peptide and kaliuretic peptide each eliminated one in six (17%) of the human squamous cell lung carcinomas. Long-acting natriuretic peptide, although it did not eliminate any of the human squamous cell lung carcinomas did decrease the volume of one carcinoma to only 2% (P < 0.0001) of the untreated carcinomas. The squamous cell lung carcinomas that were not eliminated, with the exception of the one LANP-treated tumour that decreased to only 2% of the volume of the untreated cancers, grew rapidly but their growth velocity compared to controls decreased by 76%, 40%, 38% and 25% in the vessel dilator, atrial natriuretic peptide, kaliuretic peptide and long-acting natriuretic peptide groups respectively (P < 0.05). Three of four cardiac hormones synthesized by the atrial natriuretic peptide gene can eliminate human squamous cell lung carcinomas in athymic mice when treated subcutaneously for 4 weeks. The 4th cardiac hormone, i.e. long-acting natriuretic peptide, decreased the volume of one squamous cell lung carcinoma to 2% of that of untreated animals, suggesting that it, too, has beneficial effects on squamous cell lung cancers.