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

Vesely DL - Cancers (Basel) (2011)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Departments of Internal Medicine, Molecular Pharmacology and Physiology, Cardiac Hormone Center, University of South Florida Health Sciences Center, J. A. Haley Veterans Medical Center-151, 13000 Bruce B. Downs Blvd., Tampa, Florida 33612, USA. david.vesely@va.gov.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Cardiac hormones inhibit five metabolic targets, i.e., Ras-GTP, MEK 1/2, and ERK 1/2 kinases of the Ras-MEK 1/2-ERK 1/2 kinase cascade by 95-98%. They are also strong inhibitors (i.e., 91%) of DNA synthesis within cancer cells. Reprinted with permission from [54].
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f4-cancers-03-01182: Cardiac hormones inhibit five metabolic targets, i.e., Ras-GTP, MEK 1/2, and ERK 1/2 kinases of the Ras-MEK 1/2-ERK 1/2 kinase cascade by 95-98%. They are also strong inhibitors (i.e., 91%) of DNA synthesis within cancer cells. Reprinted with permission from [54].

Mentions: ANP and LANP, likewise, decrease the activation of ERK 1/2 kinases over a concentration range of 0.01 μM to 10 μM [12]. ANP and LANP's maximal inhibition of the phosphorylation of ERK 1/2 kinases were 94% and 88% (p < 0.0001), respectively [12]. ANP had significant effects within five minutes at a concentration of 10 μM. The inhibition of ERK 1/2 kinases lasted for at least two hours, where it was maximal, secondary to ANP and LANP. Their ability to inhibit ERK 1/2 was inhibited by cyclic GMP antibody and cyclic GMP itself inhibited ERK 1/2 phosphorylation, suggesting that cyclic GMP mediates their effects of inhibition the phosphorylation of ERK 1/2 kinases [12]. Thus, the cardiac hormones inhibit five metabolic targets, i.e., Ras-GTP, MEK 1/2 kinases and ERK 1/2 kinases as illustrated in Figure 4.


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

Vesely DL - Cancers (Basel) (2011)

Cardiac hormones inhibit five metabolic targets, i.e., Ras-GTP, MEK 1/2, and ERK 1/2 kinases of the Ras-MEK 1/2-ERK 1/2 kinase cascade by 95-98%. They are also strong inhibitors (i.e., 91%) of DNA synthesis within cancer cells. Reprinted with permission from [54].
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3756409&req=5

f4-cancers-03-01182: Cardiac hormones inhibit five metabolic targets, i.e., Ras-GTP, MEK 1/2, and ERK 1/2 kinases of the Ras-MEK 1/2-ERK 1/2 kinase cascade by 95-98%. They are also strong inhibitors (i.e., 91%) of DNA synthesis within cancer cells. Reprinted with permission from [54].
Mentions: ANP and LANP, likewise, decrease the activation of ERK 1/2 kinases over a concentration range of 0.01 μM to 10 μM [12]. ANP and LANP's maximal inhibition of the phosphorylation of ERK 1/2 kinases were 94% and 88% (p < 0.0001), respectively [12]. ANP had significant effects within five minutes at a concentration of 10 μM. The inhibition of ERK 1/2 kinases lasted for at least two hours, where it was maximal, secondary to ANP and LANP. Their ability to inhibit ERK 1/2 was inhibited by cyclic GMP antibody and cyclic GMP itself inhibited ERK 1/2 phosphorylation, suggesting that cyclic GMP mediates their effects of inhibition the phosphorylation of ERK 1/2 kinases [12]. Thus, the cardiac hormones inhibit five metabolic targets, i.e., Ras-GTP, MEK 1/2 kinases and ERK 1/2 kinases as illustrated in Figure 4.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Departments of Internal Medicine, Molecular Pharmacology and Physiology, Cardiac Hormone Center, University of South Florida Health Sciences Center, J. A. Haley Veterans Medical Center-151, 13000 Bruce B. Downs Blvd., Tampa, Florida 33612, USA. david.vesely@va.gov.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus