Family of Peptides Synthesized in the Human Body Have Anticancer Effects

Four peptides synthesized in the heart, namely atrial natriuretic peptide (ANP), vessel dilator, kaliuretic peptide and long-acting natriuretic peptide (LANP), reduce cancer cells in vitro by up to 97%. These four cardiac hormones, in vivo, eliminate up to 86% of human small-cell lung carcinomas, two-thirds of human breast carcinomas, and up to 80% of human pancreatic adenocarcinomas growing in athymic mice. Their anticancer mechanisms of action, after binding to specific receptors on cancer cells, include targeting the Rat sarcoma-bound guanosine triphosphate (RAS) (95% inhibition)-mitogen activated protein kinase kinase 1/2 (MEK-1/2) (98% inhibition)-extracellular signal- related kinases 1/2 (ERK-1/2) (96% inhibition) cascade in cancer cells. They also inhibit MAPK9, i.e. c-JUN-N-terminal kinase 2. They are dual inhibitors of vascular endothelial growth factor (VEGF) and its VEGFR2 receptor (up to 89%). One of their downstream targets of VEGF is β-Catenin, which they reduce up to 88%. The Wingless-related integration site (WNT) pathway is inhibited by up to 68% and WNT secreted- Frizzled related protein-3 was reduced by up to 84% by the four peptide hormones. A serine/threonine-protein kinase, AKT, derived from "AK" mouse strain with thymomas (T), is reduced by up to 64% by the peptide hormones. Signal transducer and activator of transcription 3 (STAT3), a final "switch" that activates gene expression patterns that lead to malignancy, is decreased by up to 88% by these peptide hormones; STAT3 is specifically reduced as they do not affect STAT1. There is cross-talk between the RAS-MEK-1/2-ERK- 1/2 kinase cascade, VEGF, β-catenin, WNT, JNK and STAT pathways and each of these pathways is inhibited by the cardiac peptides. These peptides have been demonstrated to enter the nucleus of cancer cells where they inhibit the proto- oncogenes c-FOS (up to 82%) and c-JUN (up to 61%). Conclusion: The cardiac peptides inhibit multiple targets and cross-talk between the targets within cancer cells. The human body synthesizes a number of peptides that have salt-excreting (natriuretic) properties to help control blood volume by causing a natriuresis and diuresis in healthy humans (1-3) and in persons retaining salt and water such as in congestive heart failure (4, 5) and acute renal failure (6, 7). In the heart, the atrial natriuretic peptide prohormone (proANP) gene encodes a 126-amino-acid (a.a.) pro-hormone which contains four peptide hormones (3, 8, 9). These four hormones synthesized by the atrium of the heart are long-acting natriuretic peptide (LANP), which consists of the first 30 a.a. from the N-terminal end of the 126 a.a. prohormone, vessel dilator, a.a. 31-67 of this prohormone, kaliuretic peptide, a.a. 79-98; and atrial natriuretic peptide (ANP), a.a. 99-126 of this 126-a.a. pro-hormone (3, 10). These peptides were named for their most potent known biological effect(s) at the time of naming (3). These peptide hormones are now synthesized with commercial peptide synthesizers from their known a.a. sequences (3). Via a separate gene, the heart also synthesizes brain natriuretic peptide (BNP), which was misnamed, as 50-fold more BNP is made in the heart than the brain. A third gene in the heart synthesizes C-natriuretic peptide. In the kidney, the ANP pro-hormone is also synthesized but it is cleaved differently, adding four a.a. of kaliuretic