Division of Endocrinology, Diabetes and Metabolism, James A. Haley VA Medical Center and University of South Florida Cardiac Hormone Center, Tampa, FL, USA.
J Investig Med. 2013 Jun;61(5):816-22. doi: 10.2310/JIM.0b013e318292110a.
Four cardiac hormones are synthesized by the atrial natriuretic peptide prohormone gene. These hormones, namely, long-acting natriuretic peptide, vessel dilator, kaliuretic peptide, and atrial natriuretic peptide, help regulate blood pressure and blood volume by causing vasodilation, diuresis, and sodium excretion. These cardiac hormones reduce up to 97% of all cancer cells in vitro. These 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 guanosine diphosphate conversion to RAS guanosine triphosphate (95% inhibition)-mitogen-activated protein kinase kinase 1/2 (98% inhibition)-extracellular signal-related kinase 1/2 (96% inhibition) cascade in cancer cells. They also reduce c-Jun-N-terminal kinase 2 up to 89%. These multiple kinase inhibitors are also inhibitors of vascular endothelial growth factor (VEGF) and its VEGFR2 receptor (up to 89% inhibition). They reduce β-catenin up to 88%. They inhibit the WNT pathway up to 68%, and secreted Frizzled-related protein 3 is decreased up to 84%. AKT, a serine/threonine-protein kinase, is reduced up to 64% by the cardiac hormones. Signal transducer and activator of transcription 3, a final "switch" that activates gene expression that leads to malignancy, is decreased by up to 88% by the cardiac hormones. Of importance, the cross talk between the multiple kinases, VEGF, B-catenin, WNT, and STAT pathways is inhibited by the 4 cardiac hormones.
四种心激素由心房利钠肽原基因合成。这些激素，即长效利钠肽、血管扩张剂、利钾肽和心房利钠肽，通过血管扩张、利尿和钠排泄来帮助调节血压和血容量。这些心激素在体外可使高达 97%的癌细胞减少。这些心激素可消除多达 86%的人类小细胞肺癌、三分之二的人类乳腺癌和多达 80%在免疫缺陷小鼠中生长的人类胰腺腺癌。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 Rat sarcoma-bound guanosine diphosphate 转化为 RAS guanosine triphosphate（95%抑制）-mitogen-activated protein kinase kinase 1/2（98%抑制）-extracellular signal-related kinase 1/2（96%抑制）级联反应在癌细胞中。它们还可使 c-Jun-N-terminal kinase 2 减少高达 89%。这些多激酶抑制剂也是血管内皮生长因子（VEGF）及其 VEGFR2 受体的抑制剂（高达 89%抑制）。它们可使 β-catenin 减少高达 88%。它们抑制 WNT 途径高达 68%，并使分泌的 Frizzled 相关蛋白 3 减少高达 84%。AKT，一种丝氨酸/苏氨酸蛋白激酶，可被心激素减少高达 64%。信号转导和转录激活因子 3（STAT3）是一种最终的“开关”，可激活导致恶性肿瘤的基因表达，它可被心激素减少高达 88%。重要的是，多激酶、VEGF、B-catenin、WNT 和 STAT 途径之间的串扰被这 4 种心激素抑制。
