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Title:
Efficacy and mechanism of action of Deguelin in suppressing metastasis of 4T1 cells | Clinical & Experimental Metastasis
Description:
Cancer related deaths in breast cancer patients are due to metastasis of the disease. Murine 4T1 cells (Murine mammary cancer cell line developed from 6-thioguanine resistant tumor) provide an excellent research tool for metastasis related studies because these cells are highly aggressive and readily metastasize to the lungs. In this study we determined the effect of Deguelin on in vivo/vitro growth and metastasis of 4T1 cells. Deguelin inhibited the in vitro growth of 4T1 cells in a time and dose dependent manner accompanied with reduced nuclear PCNA immunostaining. In cells treated with Deguelin, reduced expression of nuclear c-Met, and its downstream targets such p-ERK and p-AKT was observed. Deguelin reduced the cell migration in 4T1 cells as determined by scratch wound assay. Combined treatment with Deguelin + ERK or PI3K/AKT inhibitor had no additional effect on cell migration. These results indicated that the action of Deguelin on cell migration may be mediated by AKT and ERK mediated signaling pathways. In vivo, Deguelin treatment significantly inhibited growth of 4T1 cells. Deguelin also reduced the occurrence of metastatic lung lesions by 33 % when cells were injected intravenously into Balb/c female mice. There was no difference in the body weight, nor was there a difference in liver and spleen weights between vehicle treated-control and Deguelin-treated animals, which indicated that Deguelin was nontoxic at the dose used in the present study. These results provide rationale for developing Deguelin as a chemotherapeutic agent for triple negative breast cancer patients.
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Keywords {🔍}
cancer, google, scholar, article, pubmed, cas, deguelin, cells, growth, factor, breast, cell, human, metastasis, receptor, lee, expression, mehta, res, lung, hepatocyte, protein, pathway, negative, apoptosis, chen, research, tumor, cmet, inhibitor, kinase, int, clin, supplementary, material, privacy, cookies, content, migration, erk, carcinoma, met, pezzuto, hong, author, publish, search, efficacy, action, patel,
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nuclear factor kappa-light-chain-enhancer month download article/chapter mouse strain ak-thymoma small-cell lung carcinomas phosphatidylinositol 3-kinase/akt pathway pyrene-induced lung tumorigenesis akash gupta di renzo mf author information authors rutulkumar patel hepatocyte growth factor induce c-met expression murine 4t1 cells human breast carcinoma c-met proto-oncogene mammary epithelial cells igf-binding protein-3 expression breast cancer patients human breast cancer full article pdf breast cancer cells nuclear c-met author correspondence wnt signaling pathway metastasis related studies human pancreatic cancer iit research institute erk protein kinase hgf/sf receptor excellent research tool privacy choices/manage cookies triple negative status metastatic lung lesions estrogen receptor negative deguelin inhibits growth lung cancer cells nf-kappab pathway 6-thioguanine resistant tumor lung tumor model akt/mtor pathway progesterone receptor negative deguelin-induced inhibition tnbc papillary thyroid carcinoma hgf-induced proliferation c-met participate hypoxia-inducible factor hypoxia inducible factor-1 met receptor expression deguelin targeting
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headline:Efficacy and mechanism of action of Deguelin in suppressing metastasis of 4T1 cells
description:Cancer related deaths in breast cancer patients are due to metastasis of the disease. Murine 4T1 cells (Murine mammary cancer cell line developed from 6-thioguanine resistant tumor) provide an excellent research tool for metastasis related studies because these cells are highly aggressive and readily metastasize to the lungs. In this study we determined the effect of Deguelin on in vivo/vitro growth and metastasis of 4T1 cells. Deguelin inhibited the in vitro growth of 4T1 cells in a time and dose dependent manner accompanied with reduced nuclear PCNA immunostaining. In cells treated with Deguelin, reduced expression of nuclear c-Met, and its downstream targets such p-ERK and p-AKT was observed. Deguelin reduced the cell migration in 4T1 cells as determined by scratch wound assay. Combined treatment with Deguelin + ERK or PI3K/AKT inhibitor had no additional effect on cell migration. These results indicated that the action of Deguelin on cell migration may be mediated by AKT and ERK mediated signaling pathways. In vivo, Deguelin treatment significantly inhibited growth of 4T1 cells. Deguelin also reduced the occurrence of metastatic lung lesions by 33 % when cells were injected intravenously into Balb/c female mice. There was no difference in the body weight, nor was there a difference in liver and spleen weights between vehicle treated-control and Deguelin-treated animals, which indicated that Deguelin was nontoxic at the dose used in the present study. These results provide rationale for developing Deguelin as a chemotherapeutic agent for triple negative breast cancer patients.
datePublished:2013-05-05T00:00:00Z
dateModified:2013-05-05T00:00:00Z
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4T1 cells
Metastasis
Biomarkers
Deguelin
TNBC
Cancer Research
Biomedicine
general
Oncology
Hematology
Surgical Oncology
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headline:Efficacy and mechanism of action of Deguelin in suppressing metastasis of 4T1 cells
description:Cancer related deaths in breast cancer patients are due to metastasis of the disease. Murine 4T1 cells (Murine mammary cancer cell line developed from 6-thioguanine resistant tumor) provide an excellent research tool for metastasis related studies because these cells are highly aggressive and readily metastasize to the lungs. In this study we determined the effect of Deguelin on in vivo/vitro growth and metastasis of 4T1 cells. Deguelin inhibited the in vitro growth of 4T1 cells in a time and dose dependent manner accompanied with reduced nuclear PCNA immunostaining. In cells treated with Deguelin, reduced expression of nuclear c-Met, and its downstream targets such p-ERK and p-AKT was observed. Deguelin reduced the cell migration in 4T1 cells as determined by scratch wound assay. Combined treatment with Deguelin + ERK or PI3K/AKT inhibitor had no additional effect on cell migration. These results indicated that the action of Deguelin on cell migration may be mediated by AKT and ERK mediated signaling pathways. In vivo, Deguelin treatment significantly inhibited growth of 4T1 cells. Deguelin also reduced the occurrence of metastatic lung lesions by 33 % when cells were injected intravenously into Balb/c female mice. There was no difference in the body weight, nor was there a difference in liver and spleen weights between vehicle treated-control and Deguelin-treated animals, which indicated that Deguelin was nontoxic at the dose used in the present study. These results provide rationale for developing Deguelin as a chemotherapeutic agent for triple negative breast cancer patients.
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4T1 cells
Metastasis
Biomarkers
Deguelin
TNBC
Cancer Research
Biomedicine
general
Oncology
Hematology
Surgical Oncology
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