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

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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.

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Acknowledgments

We thank Karen Murphy for excellent secretarial assistance. This work was supported in part by grants from the James and Esther King Florida Biomedical Research Program; the Florida Department of Health; and the Mama Mare Breast Cancer Foundation. The contents of this publication do not represent the views of the Department of Veterans Affairs or the United States Government.

Conflict of interest

Dr. Vesely has assigned the patent to treat cancer with these cardiac hormones to the University of South Florida, which has not licensed this patent to any commercial entity. There has been no pharmaceutical company funding or input into the studies described herein. All the remaining authors have declared no conflict of interest.

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Correspondence to David L. Vesely.

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Lane, M.L., Frost, C.D., Nguyen, J.P. et al. Potent selective inhibition of STAT 3 versus STAT 1 by cardiac hormones. Mol Cell Biochem 371, 209–215 (2012). https://doi.org/10.1007/s11010-012-1437-1

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  • DOI: https://doi.org/10.1007/s11010-012-1437-1

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