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

BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: Four cardiac hormones are potent inhibitors of c-Fos and c-Jun proto-oncogenes within the nucleus of cancer cells.