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

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Issue Date
2012-12
Authors
Lane, Meghan L.
Frost, Chelsea D.
Nguyen, Jennifer P.
Skelton, William P.
Skelton, Michelle
Vesely, David L.
Advisor
Citation

Lane, Meghan L.; Frost, Chelsea D.; Nguyen, Jennifer; Skelton, William P.; Skelton, Michelle; Vesely, David L. 2012. Potent selective inhibition of STAT 3 versus STAT 1 by cardiac hormones. Molecular and Cellular Biochemistry, v.371 no.1-2 pp.209-215

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 mu M 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.

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