title: Potent selective inhibition of STAT 3 versus STAT 1 by cardiac hormones.
abstract: 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.
authors.affiliation: Department of Medicine, USF Cardiac Hormone Center, James A. Haley VA Medical Center and University of South Florida, 13000 Bruce B. Downs Blvd, Tampa, FL 33612, USA. megja.vu@gmail.com
authors.forename: Meghan L
authors.initials: ML
authors.lastname: Lane
authors.forename: Chelsea D
authors.initials: CD
authors.lastname: Frost
authors.forename: Jennifer P
authors.initials: JP
authors.lastname: Nguyen
authors.forename: William P
authors.initials: WP
authors.lastname: Skelton
authors.forename: Michelle
authors.initials: M
authors.lastname: Skelton
authors.forename: David L
authors.initials: DL
authors.lastname: Vesely
mesh_terms: D000230:Adenocarcinoma; D009320:Atrial Natriuretic Factor / Q000494:pharmacology; D015153:Blotting, Western; D045744:Cell Line, Tumor; D006801:Humans; D008175:Lung Neoplasms; D010190:Pancreatic Neoplasms; D010446:Peptide Fragments / Q000494:pharmacology; D011498:Protein Precursors / Q000494:pharmacology; D050794:STAT1 Transcription Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D055752:Small Cell Lung Carcinoma
chemical_list: D010446:Peptide Fragments; D011498:Protein Precursors; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C075322:atrial natriuretic factor precursor (79-98); C054547:atrial natriuretic factor prohormone (1-30), human; C054548:atrial natriuretic factor prohormone (31-67); D009320:Atrial Natriuretic Factor