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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

Effects of black rice anthocyanins (BRACs) extract and RAF/MAPK inhibitors on phosphorylation of RAF, MEK, ERK, and JNK. MDA-MB-453 cells were treated with BRACs (0 or 200 μg/mL) with or without inhibitors ZM33672 (70 nM), U0126 (10 μM), and SP600125 (50 nM) for 24 h. Phosphorylation of (a) RAF, (b) MEK1/2, ERK1/2, and (c) JNK was determined using immunoblotting. Expression of β-actin served as an internal control.
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fig8: Effects of black rice anthocyanins (BRACs) extract and RAF/MAPK inhibitors on phosphorylation of RAF, MEK, ERK, and JNK. MDA-MB-453 cells were treated with BRACs (0 or 200 μg/mL) with or without inhibitors ZM33672 (70 nM), U0126 (10 μM), and SP600125 (50 nM) for 24 h. Phosphorylation of (a) RAF, (b) MEK1/2, ERK1/2, and (c) JNK was determined using immunoblotting. Expression of β-actin served as an internal control.

Mentions: As shown in Figure 8, treatment with inhibitors attenuated the phosphorylation of RAF1, MEK1/2, ERK1/2, and JNK. Furthermore, RAF/MAPK pathway inhibitors suppressed the expression of the various proteins in the RAF/MAPK pathway. We subsequently evaluated the effects of BRACs and RAF/MAPK pathway inhibitors on the activation of the same proteins in MDA-MB-453 cells. Strikingly, cotreatment with BRACs and MAPK inhibitors downregulated the phosphorylation of RAF/MAPK pathway proteins with a significantly greater potency than that shown by BRACs alone in MDA-MB-453 cells.


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)

Effects of black rice anthocyanins (BRACs) extract and RAF/MAPK inhibitors on phosphorylation of RAF, MEK, ERK, and JNK. MDA-MB-453 cells were treated with BRACs (0 or 200 μg/mL) with or without inhibitors ZM33672 (70 nM), U0126 (10 μM), and SP600125 (50 nM) for 24 h. Phosphorylation of (a) RAF, (b) MEK1/2, ERK1/2, and (c) JNK was determined using immunoblotting. Expression of β-actin served as an internal control.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4663286&req=5

fig8: Effects of black rice anthocyanins (BRACs) extract and RAF/MAPK inhibitors on phosphorylation of RAF, MEK, ERK, and JNK. MDA-MB-453 cells were treated with BRACs (0 or 200 μg/mL) with or without inhibitors ZM33672 (70 nM), U0126 (10 μM), and SP600125 (50 nM) for 24 h. Phosphorylation of (a) RAF, (b) MEK1/2, ERK1/2, and (c) JNK was determined using immunoblotting. Expression of β-actin served as an internal control.
Mentions: As shown in Figure 8, treatment with inhibitors attenuated the phosphorylation of RAF1, MEK1/2, ERK1/2, and JNK. Furthermore, RAF/MAPK pathway inhibitors suppressed the expression of the various proteins in the RAF/MAPK pathway. We subsequently evaluated the effects of BRACs and RAF/MAPK pathway inhibitors on the activation of the same proteins in MDA-MB-453 cells. Strikingly, cotreatment with BRACs and MAPK inhibitors downregulated the phosphorylation of RAF/MAPK pathway proteins with a significantly greater potency than that shown by BRACs alone in MDA-MB-453 cells.

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