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Heart Peptide Hormones: Adjunct and Primary Treatments of Cancer.

Abstract：

:Four heart hormones, namely atrial natriuretic peptide (ANP), long-acting natriuretic peptide (LANP), vessel dilator and kaliuretic peptide reduce up to 97% of cancer cells in vitro. These four cardiac hormones eliminate up to 80% of human pancreatic adenocarcinomas, two-thirds of human breast carcinomas and up to 86% of human small-cell lung carcinomas growing in athymic mice. ANP given intravenously for 3 hours after 'curative' lung surgery as an adjunct to surgery results in a 2-year relapse-free survival of 91% compared to 75% for those treated with surgery alone. The anticancer mechanisms of action of these peptides involve binding to receptors on the cancer cells, followed by 95% inhibition of the conversion of inactive to active rat sarcoma-bound guanosine triphosphate (RAS)-mitogen-activated protein kinase (MAPK) kinases 1/2 (MEK 1/2) (98% inhibition)-extracellular signal-related kinases 1/2 (ERK1/2) (96% inhibition) cascade in cancer cells. They are dual inhibitors of vascular endothelial growth factor (VEGF) and its VEGF2 receptor (up to 89%). They also inhibit MAPK9, i.e. c-JUN-N-terminal kinase 2. One of the downstream targets of VEGF is β-catenin, which these peptides inhibit by up to 88%. These four peptide hormones inhibit the Wingless-related integration site (WNT) pathway 68% and WNT secreted-Frizzled protein is reduced by up to 84%. Signal transducer and activator of transcription 3 (STAT3), a final 'switch' that activates gene expression that leads to malignancy, is specifically reduced up to 88% by these peptides but they do not affect STAT1. There is crosstalk between the RAS-MEK 1/2-ERK 1/2 kinase cascade, VEGF, β-catenin, JNK, WNT, and STAT pathways and each of these pathways and their crosstalk is inhibited by these peptide hormones. They enter the nucleus of cancer cells where they inhibit the proto-oncogenes c-FOS (by up to 82%) and c-JUN (by up to 61%). CONCLUSION:These multiple kinase inhibitors have both adjunct and primary anticancer effects.

journal_name

Anticancer Res

journal_title

Anticancer research

authors

Vesely DL

doi

10.21873/anticanres.11152

subject

Has Abstract

pub_date

2016-11-01 00:00:00

pages

5693-5700

issue

eissn

0250-7005

issn

1791-7530

pii

36/11/5693

journal_volume

pub_type

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Heart Peptide Hormones: Adjunct and Primary Treatments of Cancer.