Cardiac hormones target nuclear oncogenes c-Fos and c-Jun in carcinoma cells
Neil J Manimala1, Chelsea D Frost, Meghan L Lane
1Department of Medicine, James A. Haley VA Medical Center, Tampa, FL, USA.
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.
Insights
Four cardiac hormones effectively inhibit the proto-oncogenes c-Fos and c-Jun, which are crucial for cancer cell proliferation. These findings highlight potential new therapeutic strategies targeting cancer growth.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- c-Fos and c-Jun form the AP-1 transcription factor, driving genes involved in cell proliferation and cancer.
- Four cardiac hormones (long-acting natriuretic peptide, vessel dilator, kaliuretic peptide, and atrial natriuretic peptide) exhibit in vivo anticancer effects.
- These hormones inhibit key signaling pathways (Ras-MEK-ERK and STAT-3) that activate c-Fos and c-Jun.
Purpose of the Study:
- To investigate the effects of four cardiac hormones on the proto-oncogenes c-Fos and c-Jun.
- To determine the impact of these hormones on cancer cell nuclei.
Main Methods:
- Four cardiac hormones were tested for their ability to decrease c-Fos and c-Jun levels.
- Levels were measured using ELISA in extracted nuclei from three human cancer cell lines.
Main Results:
- Cardiac hormones significantly reduced c-Fos expression across hepatocellular, small-cell lung, and renal cancer cells (up to 82%).
- Vessel dilator, LANP, KP, and ANP also markedly reduced c-Jun expression in these cancer cell lines (up to 65%).
Conclusions:
- The four cardiac hormones demonstrate potent inhibitory effects on c-Fos and c-Jun proto-oncogenes.
- These hormones show promise as nuclear inhibitors in cancer cells.
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