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Black Rice Anthocyanins Suppress Metastasis of Breast Cancer Cells by Targeting RAS/RAF/MAPK Pathway.

Chen XY, Zhou J, Luo LP, Han B, Li F, Chen JY, Zhu YF, Chen W, Yu XP - Biomed Res Int (2015)

Bottom Line: Further, we found combined treatment with BRACs and RAF, MEK, or JNK inhibitors could enhance the antimetastatic activity, compared with that of each treatment.Transient transfection with small interfering RNAs (siRNAs) specific for raf, mek, and jnk inhibited their mRNA expression in MDA-MB-453 cells.Moreover, cotreatment with BRACs and siRNA induces a more remarkable inhibitory effect than that by either substance alone.

View Article: PubMed Central - PubMed

Affiliation: Department of Public Health, Chengdu Medical College, Chengdu 610500, China.

ABSTRACT
Overexpression of human epidermal growth factor receptor 2 (HER2) drives the biology of 30% of breast cancer cases. As a transducer of HER2 signaling, RAS/RAF/MAPK pathway plays a pivotal role in the development of breast cancer. In this study, we examined the molecular mechanisms underlying the chemopreventive effects of black rice anthocyanins (BRACs) extract and identified their molecular targets in HER2(+) breast cancer cells. Treatment of MDA-MB-453 cells (HER2(+)) with BRACs inhibited cell migration and invasion, suppressed the activation of mitogen-activated protein kinase kinase kinase (RAF), mitogen-activated protein kinase kinase (MEK), and c-Jun N-terminal kinase (JNK), and downregulated the secretion of matrix metalloproteinase 2 (MMP2) and MMP9. BRACs also weakened the interactions of HER2 with RAF, MEK, and JNK proteins, respectively, and decreased the mRNA expression of raf, mek, and jnk. Further, we found combined treatment with BRACs and RAF, MEK, or JNK inhibitors could enhance the antimetastatic activity, compared with that of each treatment. Transient transfection with small interfering RNAs (siRNAs) specific for raf, mek, and jnk inhibited their mRNA expression in MDA-MB-453 cells. Moreover, cotreatment with BRACs and siRNA induces a more remarkable inhibitory effect than that by either substance alone. In summary, our study suggested that BRACs suppress metastasis in breast cancer cells by targeting the RAS/RAF/MAPK pathway.

No MeSH data available.


Related in: MedlinePlus

Black rice anthocyanins (BRACs) extract and rapidly RAF/MEK/JNK inhibitors decrease migration and invasion of MDA-MB-453 cells. (a) MDA-MB-453 cells were exposed to BRACs (0 or 200 μg/mL) with or without RAF/MAPK inhibitors ZM33672 (70 nM), U0126 (10 μM), or SP600125 (50 nM) for 24 h. Cell migration was determined using wound healing migration assay and numbers of migratory cells was determined by counting using a microscope; ∗P < 0.05 versus control and #P < 0.05 versus BRACs groups. (b) MDA-MB-453 cells were plated in upper compartments of Matrigel invasion chambers and exposed to BRACs (0 or 200 μg/mL) with or without RAF/MAPK inhibitors ZM33672 (70 nM), U0126 (10 μM), or SP600125 (50 nM). ∗P < 0.05 versus control; #P < 0.05 versusBRACs groups. Data are mean ± SEM of three independent experiments.
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fig2: Black rice anthocyanins (BRACs) extract and rapidly RAF/MEK/JNK inhibitors decrease migration and invasion of MDA-MB-453 cells. (a) MDA-MB-453 cells were exposed to BRACs (0 or 200 μg/mL) with or without RAF/MAPK inhibitors ZM33672 (70 nM), U0126 (10 μM), or SP600125 (50 nM) for 24 h. Cell migration was determined using wound healing migration assay and numbers of migratory cells was determined by counting using a microscope; ∗P < 0.05 versus control and #P < 0.05 versus BRACs groups. (b) MDA-MB-453 cells were plated in upper compartments of Matrigel invasion chambers and exposed to BRACs (0 or 200 μg/mL) with or without RAF/MAPK inhibitors ZM33672 (70 nM), U0126 (10 μM), or SP600125 (50 nM). ∗P < 0.05 versus control; #P < 0.05 versusBRACs groups. Data are mean ± SEM of three independent experiments.

Mentions: The addition of the RAF/MAPK inhibitors to the cell migration and invasion assay cultures reduced the migration and invasion of the MDA-MB-453 cells (Figures 2(a) and 2(b)). Furthermore, the RAF, MEK, and JNK inhibitors increased the antimetastatic effect of BRACs.


Black Rice Anthocyanins Suppress Metastasis of Breast Cancer Cells by Targeting RAS/RAF/MAPK Pathway.

Chen XY, Zhou J, Luo LP, Han B, Li F, Chen JY, Zhu YF, Chen W, Yu XP - Biomed Res Int (2015)

Black rice anthocyanins (BRACs) extract and rapidly RAF/MEK/JNK inhibitors decrease migration and invasion of MDA-MB-453 cells. (a) MDA-MB-453 cells were exposed to BRACs (0 or 200 μg/mL) with or without RAF/MAPK inhibitors ZM33672 (70 nM), U0126 (10 μM), or SP600125 (50 nM) for 24 h. Cell migration was determined using wound healing migration assay and numbers of migratory cells was determined by counting using a microscope; ∗P < 0.05 versus control and #P < 0.05 versus BRACs groups. (b) MDA-MB-453 cells were plated in upper compartments of Matrigel invasion chambers and exposed to BRACs (0 or 200 μg/mL) with or without RAF/MAPK inhibitors ZM33672 (70 nM), U0126 (10 μM), or SP600125 (50 nM). ∗P < 0.05 versus control; #P < 0.05 versusBRACs groups. Data are mean ± SEM of three independent experiments.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4663286&req=5

fig2: Black rice anthocyanins (BRACs) extract and rapidly RAF/MEK/JNK inhibitors decrease migration and invasion of MDA-MB-453 cells. (a) MDA-MB-453 cells were exposed to BRACs (0 or 200 μg/mL) with or without RAF/MAPK inhibitors ZM33672 (70 nM), U0126 (10 μM), or SP600125 (50 nM) for 24 h. Cell migration was determined using wound healing migration assay and numbers of migratory cells was determined by counting using a microscope; ∗P < 0.05 versus control and #P < 0.05 versus BRACs groups. (b) MDA-MB-453 cells were plated in upper compartments of Matrigel invasion chambers and exposed to BRACs (0 or 200 μg/mL) with or without RAF/MAPK inhibitors ZM33672 (70 nM), U0126 (10 μM), or SP600125 (50 nM). ∗P < 0.05 versus control; #P < 0.05 versusBRACs groups. Data are mean ± SEM of three independent experiments.
Mentions: The addition of the RAF/MAPK inhibitors to the cell migration and invasion assay cultures reduced the migration and invasion of the MDA-MB-453 cells (Figures 2(a) and 2(b)). Furthermore, the RAF, MEK, and JNK inhibitors increased the antimetastatic effect of BRACs.

Bottom Line: Further, we found combined treatment with BRACs and RAF, MEK, or JNK inhibitors could enhance the antimetastatic activity, compared with that of each treatment.Transient transfection with small interfering RNAs (siRNAs) specific for raf, mek, and jnk inhibited their mRNA expression in MDA-MB-453 cells.Moreover, cotreatment with BRACs and siRNA induces a more remarkable inhibitory effect than that by either substance alone.

View Article: PubMed Central - PubMed

Affiliation: Department of Public Health, Chengdu Medical College, Chengdu 610500, China.

ABSTRACT
Overexpression of human epidermal growth factor receptor 2 (HER2) drives the biology of 30% of breast cancer cases. As a transducer of HER2 signaling, RAS/RAF/MAPK pathway plays a pivotal role in the development of breast cancer. In this study, we examined the molecular mechanisms underlying the chemopreventive effects of black rice anthocyanins (BRACs) extract and identified their molecular targets in HER2(+) breast cancer cells. Treatment of MDA-MB-453 cells (HER2(+)) with BRACs inhibited cell migration and invasion, suppressed the activation of mitogen-activated protein kinase kinase kinase (RAF), mitogen-activated protein kinase kinase (MEK), and c-Jun N-terminal kinase (JNK), and downregulated the secretion of matrix metalloproteinase 2 (MMP2) and MMP9. BRACs also weakened the interactions of HER2 with RAF, MEK, and JNK proteins, respectively, and decreased the mRNA expression of raf, mek, and jnk. Further, we found combined treatment with BRACs and RAF, MEK, or JNK inhibitors could enhance the antimetastatic activity, compared with that of each treatment. Transient transfection with small interfering RNAs (siRNAs) specific for raf, mek, and jnk inhibited their mRNA expression in MDA-MB-453 cells. Moreover, cotreatment with BRACs and siRNA induces a more remarkable inhibitory effect than that by either substance alone. In summary, our study suggested that BRACs suppress metastasis in breast cancer cells by targeting the RAS/RAF/MAPK pathway.

No MeSH data available.


Related in: MedlinePlus