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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 BRACs on the interactions of HER2 with RAF, MEK, ERK, and JNK. MCF-10A, MCF-7, and MDA-MB-453 cells were treated with BRACs (0 or 200 μg/mL) for 24 h. Cell lysates were collected and immunoprecipitated with anti-HER2 antibody and then immunoblotted with antibodies against HER2, RAF/phosphorylated (p)-RAF, MEK/p-MEK/p-ERK, and JNK/p-JNK.
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fig7: Effects of BRACs on the interactions of HER2 with RAF, MEK, ERK, and JNK. MCF-10A, MCF-7, and MDA-MB-453 cells were treated with BRACs (0 or 200 μg/mL) for 24 h. Cell lysates were collected and immunoprecipitated with anti-HER2 antibody and then immunoblotted with antibodies against HER2, RAF/phosphorylated (p)-RAF, MEK/p-MEK/p-ERK, and JNK/p-JNK.

Mentions: To determine whether the inhibitory effect of BRACs on RAF/MAPK signaling is due to the direct physical interaction of HER2 and RAF/MAPK proteins, we performed an in vitro immunoprecipitation (IP) assay. The results indicated that BRACs inhibited the interactions between HER2 and RAF1, MEK, and JNK (Figure 7). These results suggested that BRACs might bind to HER2 as well as RAF1, MEK, or JNK or all the three at allosteric sites.


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 BRACs on the interactions of HER2 with RAF, MEK, ERK, and JNK. MCF-10A, MCF-7, and MDA-MB-453 cells were treated with BRACs (0 or 200 μg/mL) for 24 h. Cell lysates were collected and immunoprecipitated with anti-HER2 antibody and then immunoblotted with antibodies against HER2, RAF/phosphorylated (p)-RAF, MEK/p-MEK/p-ERK, and JNK/p-JNK.
© Copyright Policy
Related In: Results  -  Collection

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

fig7: Effects of BRACs on the interactions of HER2 with RAF, MEK, ERK, and JNK. MCF-10A, MCF-7, and MDA-MB-453 cells were treated with BRACs (0 or 200 μg/mL) for 24 h. Cell lysates were collected and immunoprecipitated with anti-HER2 antibody and then immunoblotted with antibodies against HER2, RAF/phosphorylated (p)-RAF, MEK/p-MEK/p-ERK, and JNK/p-JNK.
Mentions: To determine whether the inhibitory effect of BRACs on RAF/MAPK signaling is due to the direct physical interaction of HER2 and RAF/MAPK proteins, we performed an in vitro immunoprecipitation (IP) assay. The results indicated that BRACs inhibited the interactions between HER2 and RAF1, MEK, and JNK (Figure 7). These results suggested that BRACs might bind to HER2 as well as RAF1, MEK, or JNK or all the three at allosteric sites.

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