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Tampa, FL, United States

Skelton IV W.P.,Duke University | Pi G.E.,University of Notre Dame | Vesely D.L.,Cardiac Hormone Center
Anticancer Research

Background: Four cardiac hormones, namely, vessel dilator, long-acting natriuretic peptide, atrial natriuretic peptide and kaliuretic peptide, have anticancer effects but whether they cause cell death of human cancer cells or normal cells is unknown. Materials and Methods: These cardiac hormones were examined for their ability to cause cell death quantified by measurement of nuclear matrix proteins 4117 which is a function of the number of dead or dying cells. Results: Each of these cardiac hormones caused cell death in up to 36% (p<0.0001) of the pancreatic adenocarcinoma cells and up to 28% (p<0.0001) of the prostate cancer cells over a concentration range of 100 pmol/l to 10 μmol/l. There was no cell death of normal human prostate, kidney, or lung cells at the above concentrations. Conclusion: Four cardiac hormones cause death of pancreatic and prostate cancer cells but not of normal prostate, lung, or kidney cells. Source

Lane M.L.,Cardiac Hormone Center | Santana O.,Cardiac Hormone Center | Frost C.D.,Cardiac Hormone Center | Nguyen J.,Wichita State University | And 4 more authors.
Anticancer Research

Background: Four cardiac peptide hormones, namely vessel dilator, long-acting natriuretic peptide (LANP), kaliuretic peptide, and atrial natriuretic peptide (ANP) have anticancer effects. Materials and Methods: The effects of these four cardiac hormones on human c-Jun-N-terminal kinase 2 (JNK2) were examined in human small cell lung cancer and human prostate cancer cells. Results: Vessel dilator, LANP, kaliuretic peptide and ANP maximally reduced expression of JNK2 by 89%, 56%, 45%, and 28%, respectively (each at p<0.0001) in human small cell lung cancer cells. In human prostate adenocarcinoma cells, JNK2 was maximally decreased 76%, 56%, 45%, (each at p<0.0001), and 28% (p<0.01) secondary to vessel dilator, LANP, kaliuretic peptide and ANP, respectively. Conclusion: These results indicate that four cardiac hormones are significant inhibitors (by up to 89%) of JNK2 in human small cell lung cancer cells and up to 76% in human prostate adenocarcinoma cells as part of their anticancer mechanism(s) of action. Source

Addisu A.,University of South Florida | Addisu A.,Cardiac Hormone Center | Gower Jr. W.R.,University of South Florida | Gower Jr. W.R.,Cardiac Hormone Center | And 5 more authors.
Experimental Biology and Medicine

Our recent study showed that intravenously administered B-type natriuretic peptide (BNP) decreases gastric emptying and intestinal absorption in mice. We aimed to test whether acute myocardial injury and heart failure have similar effects. Wildtype (WT) and natriuretic peptide receptor type A (NPR-A) knockout (KO) mice underwent cryoinfarction (myocardial infarction [MI]) of the left ventricle (LV) versus sham. LV dysfunction was confirmed by echocardiography. Percent gastric emptying and intestinal absorption were measured and analyzed one and two weeks after infarction, by gavage feeding the mice with fluorescein-isothiocyanate-dextran. Ejection fraction was 48±3% versus 64±2% (P<0.05) and fractional shortening was 24±2% versus 35±2% (P<0.01), MI versus sham, respectively. BNP levels (pg/mL) were 4292±276 one week after MI versus 105±11 in sham (n = 5, P<0.05) and 1964±755 two weeks after MI (n = 5, P<0.05). Gastric emptying was significantly decreased, 68±6% in MI versus 89±3% in sham (n = 5, P<0.05) one week after MI and 82±0.5% versus 98±0.4%, MI versus sham (n = 5, P<0.05), two weeks post-MI. Absorption, measured in relative plasma fluorescence units in WT mice, was 350±79 in MI versus 632±121 in sham (n = 6, P<0.05). KO mice did not show a significant difference in emptying or absorption compared with sham. These findings suggest that MI and LV dysfunction decrease gastric emptying and absorption in mice through a mechanism that involves NPR-A. © 2011 by the Society for Experimental Biology and Medicine. Source

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