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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

Vessel dilator at 10 μM inhibits 98% of the phosphorylation of mitogen-activated protein kinase kinase (MEK 1/2), which was maximal at two hours and significant at p < 0.00001 when evaluated by analysis of variance (ANOVA). MEK 1/2 is at 45 kDa while B-actin (loading control) is 42 kDa. The relative intensity in the bar graphs is a comparison against untreated MEK 1/2 (100% intensity). Reprinted with permission from [9].
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f3-cancers-03-01182: Vessel dilator at 10 μM inhibits 98% of the phosphorylation of mitogen-activated protein kinase kinase (MEK 1/2), which was maximal at two hours and significant at p < 0.00001 when evaluated by analysis of variance (ANOVA). MEK 1/2 is at 45 kDa while B-actin (loading control) is 42 kDa. The relative intensity in the bar graphs is a comparison against untreated MEK 1/2 (100% intensity). Reprinted with permission from [9].

Mentions: Vessel dilator and kaliuretic peptide decrease the activation of MEK 1/2 over a concentration range of 0.01 μM to 10 μM [9]. Vessel dilator and kaliuretic peptide (each 10 μM) inhibited the phosphorylation of MEK 1/2 kinase by 98% (p < 0.0001) (Figure 3) and 81% (p < 0.001), respectively [9]. The inhibition of MEK 1/2 lasted for at least two hours, where it was maximal, secondary to both peptides [9]. Their ability to inhibit MEK 1/2 was inhibited by cyclic GMP antibody and cyclic GMP itself inhibited MEK 1/2 phosphorylation, suggesting that cyclic GMP was important for mediating these cardiac hormones' effects [9].


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

Vesely DL - Cancers (Basel) (2011)

Vessel dilator at 10 μM inhibits 98% of the phosphorylation of mitogen-activated protein kinase kinase (MEK 1/2), which was maximal at two hours and significant at p < 0.00001 when evaluated by analysis of variance (ANOVA). MEK 1/2 is at 45 kDa while B-actin (loading control) is 42 kDa. The relative intensity in the bar graphs is a comparison against untreated MEK 1/2 (100% intensity). Reprinted with permission from [9].
© Copyright Policy
Related In: Results  -  Collection

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

f3-cancers-03-01182: Vessel dilator at 10 μM inhibits 98% of the phosphorylation of mitogen-activated protein kinase kinase (MEK 1/2), which was maximal at two hours and significant at p < 0.00001 when evaluated by analysis of variance (ANOVA). MEK 1/2 is at 45 kDa while B-actin (loading control) is 42 kDa. The relative intensity in the bar graphs is a comparison against untreated MEK 1/2 (100% intensity). Reprinted with permission from [9].
Mentions: Vessel dilator and kaliuretic peptide decrease the activation of MEK 1/2 over a concentration range of 0.01 μM to 10 μM [9]. Vessel dilator and kaliuretic peptide (each 10 μM) inhibited the phosphorylation of MEK 1/2 kinase by 98% (p < 0.0001) (Figure 3) and 81% (p < 0.001), respectively [9]. The inhibition of MEK 1/2 lasted for at least two hours, where it was maximal, secondary to both peptides [9]. Their ability to inhibit MEK 1/2 was inhibited by cyclic GMP antibody and cyclic GMP itself inhibited MEK 1/2 phosphorylation, suggesting that cyclic GMP was important for mediating these cardiac hormones' effects [9].

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