Division of Endocrinology, Diabetes and Metabolism, Departments of Medicine, Molecular Pharmacology and Physiology, James A. Haley VA Medical Center-151, University of South Florida Cardiac Hormone Center, Tampa, Florida 33612, USA.
Endocr Relat Cancer. 2013 May 30;20(3):R113-25. doi: 10.1530/ERC-13-0054. Print 2013 Jun.
Four cardiac hormones, namely atrial natriuretic peptide, vessel dilator, kaliuretic peptide, and long-acting natriuretic peptide, reduce up to 97% of all cancer cells in vitro. These four cardiac hormones eliminate up to 86% of human small-cell lung carcinomas, two-thirds of human breast cancers, 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 GTP (RAS) (95% inhibition)-mitogen-activated protein kinase kinase 1/2 (MEK 1/2) (98% inhibition)-extracellular signal-related kinase 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 the downstream targets of VEGF is β-catenin, which they reduce up to 88%. The WNT pathway is inhibited up to 68% and secreted frizzled-related protein 3 decreased up to 84% by the four cardiac hormones. AKT, a serine/threonine protein kinase, is reduced up to 64% by the cardiac hormones. STAT3, a final 'switch' that activates gene expression that leads to malignancy, is decreased by up to 88% by the cardiac hormones. STAT3 is specifically decreased as they do not affect STAT1. There is a 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 hormones.
四种心脏激素，即心钠肽、血管扩张剂、利钾肽和长效利钠肽，可使体外 97%的癌细胞减少。这四种心脏激素可消除多达 86%的人小细胞肺癌、三分之二的人乳腺癌和多达 80%在无胸腺小鼠中生长的人胰腺腺癌。它们的抗癌作用机制是与癌细胞上的特定受体结合后，包括靶向大鼠肉瘤结合 GTP（RAS）（95%抑制）-丝裂原活化蛋白激酶激酶 1/2（MEK 1/2）（98%抑制）-细胞外信号相关激酶 1/2（ERK 1/2）（96%抑制）级联在癌细胞中。它们还抑制 MAPK9，即 c-Jun N 端激酶 2。它们是血管内皮生长因子（VEGF）及其 VEGFR2 受体的双重抑制剂（高达 89%）。VEGF 的下游靶点之一是β-连环蛋白，它们可将其减少 88%。WNT 途径被抑制高达 68%，分泌卷曲相关蛋白 3 减少高达 84%的四种心脏激素。丝氨酸/苏氨酸蛋白激酶 AKT 被心脏激素减少高达 64%。STAT3 是一种最终的“开关”，可激活导致恶性肿瘤的基因表达，被心脏激素降低高达 88%。STAT3 特异性降低，因为它们不影响 STAT1。RAS-MEK 1/2-ERK 1/2 激酶级联、VEGF、β-连环蛋白、WNT、JNK 和 STAT 途径之间存在交叉对话，这些途径都被心脏激素抑制。
