Primary Malignant Tumors of the Heart: Four Cardiovascular Hormones Decrease the Number and DNA Synthesis of Human Angiosarcoma Cells

Vesely, Brian; Alli, Abdel A.; Song, Shijie; Sanchez‐Ramos, Juan; Fitz, Shannon R.; Gower, William R.; Vesely, David L.

doi:10.1159/000091816

Cited by 13 publications

(9 citation statements)

References 63 publications

(75 reference statements)

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“…Total protein (25 g) was subjected to SDS-PAGE, Western blotting, and densitometric analysis as previously described (5,8,13,(45)(46)(47). Blots were blocked in 5% nonfat dry milk in TBS at RT for 60 min.…”

Section: Methodsmentioning

confidence: 99%

“…NPR-C functions as a homodimer and plays an important role in the clearance of natriuretic peptides (NPs) from circulation (23). Unlike the guanylyl cyclase-coupled natriuretic peptide receptors (NPRs)-A (NPR-A) and -B (NPR-B), NPR-C is widely expressed (5,8,12,13,(45)(46)(47) and binds NPs with similar affinity (36). NPR-C consists of a short 37 amino acid cytoplasmic domain that has been reported to contain G protein-activating sequences (33,49) to allow for inhibitory guanine nucleotide regulatory protein (Gi)-dependent signal transduction (28).…”

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confidence: 99%

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The C type natriuretic peptide receptor tethers AHNAK1 at the plasma membrane to potentiate arachidonic acid-induced calcium mobilization

Alli

Gower

2009

American Journal of Physiology-Cell Physiology

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Section: Methodsmentioning

confidence: 99%

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confidence: 99%

The C type natriuretic peptide receptor tethers AHNAK1 at the plasma membrane to potentiate arachidonic acid-induced calcium mobilization

Alli

Gower

2009

American Journal of Physiology-Cell Physiology

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“…19 Each of the 4 cardiac hormones similarly reduce human pancreatic, 20 colon, 21 breast, 22 renal, 23 small-cell lung, 24 squamous cell lung, 25 and ovarian carcinomas. 26 Less common tumors such as medullary thyroid carcinomas, 27 angiosarcomas of the heart, 28 melanomas, 29 and glioblastomas of the brain 30 are likewise decreased in vitro secondary to the 4 cardiac hormones. ANP also decreases hepatoblastoma cells in culture, but the other cardiac hormones’ effects have not been investigated on hepatoblastoma cells.…”

Section: Cardiac Hormones For the Treatment Of Cancermentioning

confidence: 99%

Natriuretic Peptides’ Metabolic Targets for Treatment of Cancer

Vesely

2013

Journal of Investigative Medicine

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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.

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“…The four cardiac hormones from the ANP prohormone decrease up to 97% of human pancreatic, colon, prostate, breast, ovarian and kidney adenocarcinoma cells [26-31], angiosarcoma of the heart cells [32], melanomas [33], medullary thyroid carcinomas [34], glioblastomas of brain [35], as well as small-cell [36] and squamous cell lung carcinoma cells [37] in cell culture within 24 hours. There was a 97.4%, 87%, 88% and 89% (p < 0.001 for each) decrease of human prostate adenocarcinoma cells secondary to vessel dilator, long-acting natriuretic peptide, kaliuretic peptide, and atrial natriuretic peptide, respectively, within 24 hours at their 1 mM concentrations, without any proliferation in the three days following this decrease [28].…”

Section: Cardiac Peptides' Effects On Cancer Cells In Vitromentioning

confidence: 99%

Cardiac Hormones Target the Ras-MEK 1/2-ERK 1/2 Kinase Cancer Signaling Pathways

Vesely

2011

Cancers

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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.

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Primary Malignant Tumors of the Heart: Four Cardiovascular Hormones Decrease the Number and DNA Synthesis of Human Angiosarcoma Cells

Cited by 13 publications

References 63 publications

The C type natriuretic peptide receptor tethers AHNAK1 at the plasma membrane to potentiate arachidonic acid-induced calcium mobilization

The C type natriuretic peptide receptor tethers AHNAK1 at the plasma membrane to potentiate arachidonic acid-induced calcium mobilization

Natriuretic Peptides’ Metabolic Targets for Treatment of Cancer

Cardiac Hormones Target the Ras-MEK 1/2-ERK 1/2 Kinase Cancer Signaling Pathways

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