Departments of Medicine, Molecular Pharmacology and Physiology, and Cardiac Hormone Center, James A. Haley Veterans Medical Center and University of South Florida Health Sciences Center, Tampa, Florida 33612, USA.
Curr Pharm Des. 2010;16(9):1159-66. doi: 10.2174/138161210790963887.
The heart is a sophisticated endocrine gland synthesizing a family of peptide hormones by three different genes. These cardiac hormones are stored as 3 prohormones, i.e. atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) prohormones. Within the ANP prohormones are 4 peptide hormones, i.e. atrial natriuretic peptide, vessel dilator, kaliuretic peptide and long-acting natriuretic peptide (LANP) 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 within 24 hours in cell culture. In vivo these 4 cardiac hormones eliminate up to 80% of human pancreatic adenocarcinomas, 2/3rds of human breast cancers, and up to 86% of human small-cell lung cancers in athymic mice. Their anticancer mechanism(s) target the Ras-MEK 1/2-ERK 1/2 kinase cascade in cancer cells. These 4 cardiac hormones inhibit up to 95% of the basal activity of Ras, 98% of the phosphorylation of MEK 1/2 and 97% of the activation of basal activity of ERK 1/2. They also completely block the activity of mitogens such as epidermal growth factor's ability to stimulate ERK. 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 immunfluorescence to inhibit DNA synthesis within cancer cells.
心脏是一种复杂的内分泌腺，通过三个不同的基因合成一组肽类激素。这些心脏激素被储存为 3 种前激素，即心房利钠肽 (ANP)、脑利钠肽 (BNP) 和 C 型利钠肽 (CNP) 前激素。在 ANP 前激素中，有 4 种肽类激素，即心房利钠肽、血管扩张剂、利钾肽和长效利钠肽 (LANP)，它们在细胞培养中可在 24 小时内使高达 97%的人类胰腺、乳腺、结肠、前列腺、肾脏和卵巢癌以及小细胞和鳞状细胞肺癌细胞减少，在体内，这 4 种心脏激素可消除高达 80%的人类胰腺腺癌、2/3 的人类乳腺癌和高达 86%的人类小细胞肺癌在无胸腺小鼠中。它们的抗癌机制针对癌细胞中的 Ras-MEK 1/2-ERK 1/2 激酶级联。这 4 种心脏激素可抑制高达 95%的 Ras 基础活性、98%的 MEK 1/2 磷酸化和 97%的 ERK 1/2 基础活性的激活。它们还完全阻断丝裂原如表皮生长因子刺激 ERK 的活性。它们不会抑制健康细胞如人成纤维细胞中 ERK 的活性。它们抗癌作用机制的最后一步是，如免疫荧光所示，它们进入细胞核，抑制癌细胞内的 DNA 合成。
