Inhibition of NF-κB Activity Decreases the VEGF mRNA Expression in MDA-MB-231 Breast Cancer Cells

Shibata, Arihiro; Nagaya, Takashi; Imai, Tsuneo; Funahashi, Hiroomi; Nakao, Akimasa; Seo, Hisao

doi:10.1023/a:1015872531675

Cited by 160 publications

(113 citation statements)

References 29 publications

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“…Many reports indicated that in Akt signaling, pAkt, NF-jB, EGF, VEGF, VEGFR1, MMP-9 and MMP-2 play important roles in promoting proliferation, migration, invasion, angiogenesis, and metastasis of cancer cells (Price et al 1999;Helbig et al 2003;Rolli et al 2003;Koivunen et al1999;Kletsas et al 2000;John and Tuszynski 2001;Shibata et al 2002;Gibson et al 2002;Lee et al 2007). Thus, we next investigated if the suppression of the cancer cell shown as mean ± SD is relative to that of 0 lg/mL (0.1% DMSO vehicle) or 0 h as the control (designated as 100%).…”

Section: Resultsmentioning

confidence: 99%

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Matrine suppresses breast cancer cell proliferation and invasion via VEGF-Akt-NF-κB signaling

et al. 2009

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Matrine has shown therapeutic and/or adjuvant therapeutic effects on the treatment of some patients with breast cancer. However, its mechanisms of action are largely unknown. To disclose the mechanisms, we investigated in vitro and ex vivo effects of matrine on the cancer cells. Our results confirmed that matrine significantly suppressed the proliferation of highly-metastatic human breast cancer MDA-MB-231 cell line. Matrine displayed synergistic effects with existing anticancer agents celecoxib (the inhibitor of cyclooxygenase-2), trichostatin A (the histone deacetylase inhibitor) and rosiglitazone against the proliferation and VEGF excretions in MDA-MB-231 cells. Matrine induced the apoptosis and cell cycle arrest by reducing the ratios of Bcl-2/Bax protein and mRNA levels in the cancer cells. Matrine significantly reduced the invasion, MMP-9/MMP-2 activation, Akt phosphorylation, nuclear factor jB p-65 expression and DNA binding activity, and mRNA levels of MMP-9, MMP-2, EGF and VEGFR1 in MDA-MB-231 cells. Collectively, our results suggest that matrine inhibits the cancer cell proliferation and invasion via EGF/ VEGF-VEGFR1-Akt-NF-jB signaling pathway.

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Section: Resultsmentioning

confidence: 99%

“…Inhibition of NF-jB activity decreases the VEGF mRNA expression in MDA-MB-231 (Shibata et al 2002). NF-jB is a nuclear transcription regulator with a specific motif for bcl-2 transcription (Marsden et al 2002;Wang et al 1996).…”

Section: Resultsmentioning

confidence: 99%

Matrine suppresses breast cancer cell proliferation and invasion via VEGF-Akt-NF-κB signaling

et al. 2009

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“…Gene products that have been linked with invasion (MMP-9) and angiogenesis [vascular endothelial growth factor (VEGF)] are known to be regulated by NF-nB (40,41). We examined whether expression of these gene products is modulated by pinitol.…”

Section: Pinitol Suppresses Tnf-induced Nf-kb-dependent Gene Productsmentioning

confidence: 99%

Pinitol targets nuclear factor-κB activation pathway leading to inhibition of gene products associated with proliferation, apoptosis, invasion, and angiogenesis

Sethi

Ahn

Sung

et al. 2008

Molecular Cancer Therapeutics

122

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Pinitol (3-O-methyl-chiroinositol), a component of traditional Ayurvedic medicine (talisapatra), has been shown to exhibit anti-inflammatory and antidiabetic activities through undefined mechanisms. Because the transcription factor nuclear factor-KB (NF-KB) has been linked with inflammatory diseases, including insulin resistance, we hypothesized that pinitol must mediate its effects through modulation of NF-KB activation pathway. We found that pinitol suppressed NF-KB activation induced by inflammatory stimuli and carcinogens. This suppression was not specific to cell type. Besides inducible, pinitol also abrogated constitutive NF-KB activation noted in most tumor cells. The suppression of NF-KB activation by pinitol occurred through inhibition of the activation of IKBA kinase, leading to sequential suppression of IKBA phosphorylation, IKBA degradation, p65 phosphorylation, p65 nuclear translocation, and NF-KB-dependent reporter gene expression. Pinitol also suppressed the NF-KB reporter activity induced by tumor necrosis factor receptor (TNFR)-1, TNFR-associated death domain, TNFR-associated factor-2, transforming growth factor-B -activated kinase-1 (TAK-1)/TAK1-binding protein-1, and IKBA kinase but not that induced by p65. The inhibition of NF-KB activation thereby led to down-regulation of gene products involved in inflammation (cyclooxygenase-2), proliferation (cyclin D1 and c-myc), invasion (matrix metalloproteinase-9), angiogenesis (vascular endothelial growth factor), and cell survival (cIAP1, cIAP2, X-linked inhibitor apoptosis protein, Bcl-2, and Bcl-xL). Suppression of these gene products by pinitol enhanced the apoptosis induced by TNF and chemotherapeutic agents and suppressed TNFinduced cellular invasion. Our results show that pinitol inhibits the NF-KB activation pathway, which may explain its ability to suppress inflammatory cellular responses.

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“…NF-kB has an important role in cell cycle regulation 39 and may participate in the invasion/metastasis of breast cancer by upregulation of vascular endothelial growth factor mRNA 40 and matrix metalloproteinases. 41 Coincident expression of p50 and p65 in 13% of our tumors suggests the activation of this NF-kB heterodimer in basal breast carcinomas.…”

Section: Heterogeneity In Basal Breast Carcinomas E Lerma Et Almentioning

confidence: 99%

Immunohistochemical heterogeneity of breast carcinomas negative for estrogen receptors, progesterone receptors and Her2/neu (basal-like breast carcinomas)

et al. 2007

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Basal breast carcinomas triple negative for estrogen receptors, progesterone receptors and Her2/neu breast carcinomas are more aggressive than conventional neoplasms. We studied 64 cases with immunohistochemistry, using 23 antibodies, to characterize diverse pathological pathways. A basal cytokeratin was identified in 81% of tumors and vimentin was identified in 55%. The mean Ki67 index was 46% (range, 10-90%). Coincident expression of p50 and p65, which suggests an active nuclear factor-jB factor, was present in 13% of neoplasms. Epithelial growth factor receptor (EGFR), insulin-like growth factor-I receptor (IGF-IR) or c-kit (CD117) was identified in 77% of tumors. Loss of protein tyrosine phosphatase was found in 14%, whereas Akt activation was present in 28%. Several differences were identified between two subtypes of basal breast carcinomas: the pure variant (negative S-100 and actin) was more frequently associated with 'in situ carcinoma' (P ¼ 0.019) and pBad overexpression (P ¼ 0.098), whereas the myoepithelial variant (positive S-100 or actin) showed more frequent tumor necrosis (P ¼ 0.048), vimentin expression (P ¼ 0.0001), CD117 expression (P ¼ 0.001) and activated caspase-3 (P ¼ 0.089). IGF-IR could be as important as EGFR for the growth of these neoplasms. Basal cell carcinoma has at least two subtypes with distinct microscopic and immunohistochemical features.

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Inhibition of NF-κB Activity Decreases the VEGF mRNA Expression in MDA-MB-231 Breast Cancer Cells

Cited by 160 publications

References 29 publications

Matrine suppresses breast cancer cell proliferation and invasion via VEGF-Akt-NF-κB signaling

Matrine suppresses breast cancer cell proliferation and invasion via VEGF-Akt-NF-κB signaling

Pinitol targets nuclear factor-κB activation pathway leading to inhibition of gene products associated with proliferation, apoptosis, invasion, and angiogenesis

Immunohistochemical heterogeneity of breast carcinomas negative for estrogen receptors, progesterone receptors and Her2/neu (basal-like breast carcinomas)

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