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 decrease up to 97% of human pancreatic, breast, colon, prostate, kidney and ovarian
carcinomas as well as small-cell and squamous cell
lung cancer cells in cell culture. In vivo, these four cardiac
hormones eliminate up to 80% of human pancreatic
adenocarcinomas, two-thirds of human breast
cancers, and up to 86% of human small-cell
lung cancers growing in athymic mice. Their signaling in
cancer cells includes inhibition of up to 95% of the basal activity of Ras, 98% inhibition of the phosphorylation of the
MEK 1/2
kinases and 97% 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. They do not inhibit the activity of ERK in healthy cells such as human fibroblasts. The final step in their anticancer mechanism of action is that they enter the nucleus as demonstrated by immunocytochemical studies to inhibit
DNA synthesis within
cancer cells.