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Glaucine inhibits breast cancer cell migration and invasion by inhibiting MMP-9 gene expression through the suppression of NF-κB activation.

Kang H, Jang SW, Pak JH, Shim S - Mol. Cell. Biochem. (2015)

Bottom Line: We further show that glaucine significantly blocks phorbol 12-myristate 13-acetate (PMA)-induced MMP-9 expression and activity in a dose-dependent manner.Moreover, glaucine attenuates PMA-induced IκBα degradation and nuclear translocation of NF-κB.Taken together, our findings indicate that the MMP-9 inhibitory activity of glaucine and its abilities to attenuate IκBα and NF-κB activities may be therapeutically useful as a novel means of controlling breast cancer growth and invasiveness.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul, 138-736, Republic of Korea.

ABSTRACT
Matrix metalloproteinase-9 (MMP-9) plays a central role in the invasion and metastasis of various types of cancer cells. Here, we demonstrate that glaucine, an alkaloid isolated from the plant Corydalis turtschaninovii tuber (Papaveraceae), can inhibit the migration and invasion of human breast cancer cells. We further show that glaucine significantly blocks phorbol 12-myristate 13-acetate (PMA)-induced MMP-9 expression and activity in a dose-dependent manner. Results from reporter gene and electrophoretic mobility shift assays revealed that glaucine inhibits MMP-9 expression by suppressing activation of the nuclear transcription factor nuclear factor-κB (NF-κB). Moreover, glaucine attenuates PMA-induced IκBα degradation and nuclear translocation of NF-κB. Finally, we also found that glaucine inhibits invasion and MMP-9 expression in the highly metastatic MDA-MB-231 breast cancer cell line. Taken together, our findings indicate that the MMP-9 inhibitory activity of glaucine and its abilities to attenuate IκBα and NF-κB activities may be therapeutically useful as a novel means of controlling breast cancer growth and invasiveness.

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Glaucine inhibits the migration and invasion of PMA-treated MCF-7 cells. a PMA-induced MCF-7 cells were scratched with a pipette tip and incubated with the indicated concentration of glaucine for 36 h. The wound area was quantified by measuring the cell-free area. Original magnification was × 100. Scale bars, 100 μm. Cell migration into the wound area is represented as the percentage of recovery relative to 0 h. #P < 0.01 versus vehicle alone-treated cells, *P < 0.01 versus PMA alone-treated cells. b MCF-7 cells were incubated with 100-nM PMA and the indicated concentration of glaucine for 36 h. The invasion ability of MCF-7 cells was determined by a Matrigel invasion assay. Original magnification was × 200. Scale bars, 100 μm. The cell invasion ability was quantified; #P < 0.01 versus vehicle alone-treated cells, *P < 0.01 versus PMA alone-treated cells. Data represent the mean ± SE of three independent experiments
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Fig2: Glaucine inhibits the migration and invasion of PMA-treated MCF-7 cells. a PMA-induced MCF-7 cells were scratched with a pipette tip and incubated with the indicated concentration of glaucine for 36 h. The wound area was quantified by measuring the cell-free area. Original magnification was × 100. Scale bars, 100 μm. Cell migration into the wound area is represented as the percentage of recovery relative to 0 h. #P < 0.01 versus vehicle alone-treated cells, *P < 0.01 versus PMA alone-treated cells. b MCF-7 cells were incubated with 100-nM PMA and the indicated concentration of glaucine for 36 h. The invasion ability of MCF-7 cells was determined by a Matrigel invasion assay. Original magnification was × 200. Scale bars, 100 μm. The cell invasion ability was quantified; #P < 0.01 versus vehicle alone-treated cells, *P < 0.01 versus PMA alone-treated cells. Data represent the mean ± SE of three independent experiments

Mentions: Cell migration is a critical process during many stages of cancer cell metastasis [18]. We, therefore, determined whether glaucine inhibited the invasive behavior of breast cancer cells. As shown in Fig. 2a, glaucine significantly suppressed the migration of PMA-treated MCF-7 cells. To further explore the effect of glaucine on invasion, PMA-induced cells were treated with glaucine (15 or 30 μM), and cell invasion was determined after 36 h. As shown in Fig. 2b, glaucine markedly decreased PMA-induced MCF-7 cell invasion in a dose-dependent manner, indicating that glaucine is an effective inhibitor of breast cancer cell migration and invasion.Fig. 2


Glaucine inhibits breast cancer cell migration and invasion by inhibiting MMP-9 gene expression through the suppression of NF-κB activation.

Kang H, Jang SW, Pak JH, Shim S - Mol. Cell. Biochem. (2015)

Glaucine inhibits the migration and invasion of PMA-treated MCF-7 cells. a PMA-induced MCF-7 cells were scratched with a pipette tip and incubated with the indicated concentration of glaucine for 36 h. The wound area was quantified by measuring the cell-free area. Original magnification was × 100. Scale bars, 100 μm. Cell migration into the wound area is represented as the percentage of recovery relative to 0 h. #P < 0.01 versus vehicle alone-treated cells, *P < 0.01 versus PMA alone-treated cells. b MCF-7 cells were incubated with 100-nM PMA and the indicated concentration of glaucine for 36 h. The invasion ability of MCF-7 cells was determined by a Matrigel invasion assay. Original magnification was × 200. Scale bars, 100 μm. The cell invasion ability was quantified; #P < 0.01 versus vehicle alone-treated cells, *P < 0.01 versus PMA alone-treated cells. Data represent the mean ± SE of three independent experiments
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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Fig2: Glaucine inhibits the migration and invasion of PMA-treated MCF-7 cells. a PMA-induced MCF-7 cells were scratched with a pipette tip and incubated with the indicated concentration of glaucine for 36 h. The wound area was quantified by measuring the cell-free area. Original magnification was × 100. Scale bars, 100 μm. Cell migration into the wound area is represented as the percentage of recovery relative to 0 h. #P < 0.01 versus vehicle alone-treated cells, *P < 0.01 versus PMA alone-treated cells. b MCF-7 cells were incubated with 100-nM PMA and the indicated concentration of glaucine for 36 h. The invasion ability of MCF-7 cells was determined by a Matrigel invasion assay. Original magnification was × 200. Scale bars, 100 μm. The cell invasion ability was quantified; #P < 0.01 versus vehicle alone-treated cells, *P < 0.01 versus PMA alone-treated cells. Data represent the mean ± SE of three independent experiments
Mentions: Cell migration is a critical process during many stages of cancer cell metastasis [18]. We, therefore, determined whether glaucine inhibited the invasive behavior of breast cancer cells. As shown in Fig. 2a, glaucine significantly suppressed the migration of PMA-treated MCF-7 cells. To further explore the effect of glaucine on invasion, PMA-induced cells were treated with glaucine (15 or 30 μM), and cell invasion was determined after 36 h. As shown in Fig. 2b, glaucine markedly decreased PMA-induced MCF-7 cell invasion in a dose-dependent manner, indicating that glaucine is an effective inhibitor of breast cancer cell migration and invasion.Fig. 2

Bottom Line: We further show that glaucine significantly blocks phorbol 12-myristate 13-acetate (PMA)-induced MMP-9 expression and activity in a dose-dependent manner.Moreover, glaucine attenuates PMA-induced IκBα degradation and nuclear translocation of NF-κB.Taken together, our findings indicate that the MMP-9 inhibitory activity of glaucine and its abilities to attenuate IκBα and NF-κB activities may be therapeutically useful as a novel means of controlling breast cancer growth and invasiveness.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul, 138-736, Republic of Korea.

ABSTRACT
Matrix metalloproteinase-9 (MMP-9) plays a central role in the invasion and metastasis of various types of cancer cells. Here, we demonstrate that glaucine, an alkaloid isolated from the plant Corydalis turtschaninovii tuber (Papaveraceae), can inhibit the migration and invasion of human breast cancer cells. We further show that glaucine significantly blocks phorbol 12-myristate 13-acetate (PMA)-induced MMP-9 expression and activity in a dose-dependent manner. Results from reporter gene and electrophoretic mobility shift assays revealed that glaucine inhibits MMP-9 expression by suppressing activation of the nuclear transcription factor nuclear factor-κB (NF-κB). Moreover, glaucine attenuates PMA-induced IκBα degradation and nuclear translocation of NF-κB. Finally, we also found that glaucine inhibits invasion and MMP-9 expression in the highly metastatic MDA-MB-231 breast cancer cell line. Taken together, our findings indicate that the MMP-9 inhibitory activity of glaucine and its abilities to attenuate IκBα and NF-κB activities may be therapeutically useful as a novel means of controlling breast cancer growth and invasiveness.

Show MeSH
Related in: MedlinePlus