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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 combined with raf-, mek-, or jnk-small interfering RNAs (siRNA) decreased mRNA expression of respective genes in MDA-MB-453 cells. MDA-MB-453 cells were treated with BRACs (0 or 200 μg/mL) with or without raf-, mek-, or jnk-siRNAs for 24 h. mRNA expression of (a) raf, (b) mek, (c) jnk was measured using quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). ∗P < 0.05; data are mean ± SEM of three independent experiments.
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fig5: Black rice anthocyanins (BRACs) extract combined with raf-, mek-, or jnk-small interfering RNAs (siRNA) decreased mRNA expression of respective genes in MDA-MB-453 cells. MDA-MB-453 cells were treated with BRACs (0 or 200 μg/mL) with or without raf-, mek-, or jnk-siRNAs for 24 h. mRNA expression of (a) raf, (b) mek, (c) jnk was measured using quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). ∗P < 0.05; data are mean ± SEM of three independent experiments.

Mentions: To confirm the molecular mechanisms underlying the antimetastatic effects of BRACs, we investigated whether treatment with BRACs inhibited the mRNA expression of raf1, mek, and jnk in HER2+ breast cancer cells. As shown in Figure 4, we observed significant inhibition of raf1, mek, and jnk expression in siRNA-treated MDA-MB-453 cells. More interestingly, the expression of these genes was further reduced significantly when BRACs was applied in combination with the siRNAs (Figure 5).


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 combined with raf-, mek-, or jnk-small interfering RNAs (siRNA) decreased mRNA expression of respective genes in MDA-MB-453 cells. MDA-MB-453 cells were treated with BRACs (0 or 200 μg/mL) with or without raf-, mek-, or jnk-siRNAs for 24 h. mRNA expression of (a) raf, (b) mek, (c) jnk was measured using quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). ∗P < 0.05; data are mean ± SEM of three independent experiments.
© Copyright Policy
Related In: Results  -  Collection

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

fig5: Black rice anthocyanins (BRACs) extract combined with raf-, mek-, or jnk-small interfering RNAs (siRNA) decreased mRNA expression of respective genes in MDA-MB-453 cells. MDA-MB-453 cells were treated with BRACs (0 or 200 μg/mL) with or without raf-, mek-, or jnk-siRNAs for 24 h. mRNA expression of (a) raf, (b) mek, (c) jnk was measured using quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). ∗P < 0.05; data are mean ± SEM of three independent experiments.
Mentions: To confirm the molecular mechanisms underlying the antimetastatic effects of BRACs, we investigated whether treatment with BRACs inhibited the mRNA expression of raf1, mek, and jnk in HER2+ breast cancer cells. As shown in Figure 4, we observed significant inhibition of raf1, mek, and jnk expression in siRNA-treated MDA-MB-453 cells. More interestingly, the expression of these genes was further reduced significantly when BRACs was applied in combination with the siRNAs (Figure 5).

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