The heart is a sophisticated endocrine gland synthesizing the atrial natriuretic peptide prohormone which contains four peptide hormones, i.e. atrial natriuretic peptide, vessel dilator, kaliuretic peptide and long-acting natriuretic peptide, which eliminate up to 80% of human pancreatic cancers growing in mice. Their signaling in human pancreatic cancer cells after binding to their specific receptors includes inhibition of up to 95% of the basal activity of Ras, 98% inhibition of the phosphorylation of the MEK 1/2 kinases and 96% inhibition of the activation of basal activity of the ERK 1/2 kinases mediated via the intracellular messenger cyclic GMP. They also completely block the activity of mitogens such as epidermal growth factor’s ability to stimulate ERK and Ras. The final step in their anticancer mechanism of action is that they enter the nucleus to inhibit DNA synthesis within cancer cells, which is also mediated by cyclic GMP. These cardiac hormones cause cell death of pancreatic cancer cells but not of cells from healthy individuals. The present review provides up-to-date information on 4 new potential treatments (cardiac hormones) of pancreatic cancer and their molecular targets (Ras-MEK 1/2-ERK 1/2 kinase cascade).
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