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Cyanidin-3-glucoside inhibits ethanol-induced invasion of breast cancer cells overexpressing ErbB2.

Xu M, Bower KA, Wang S, Frank JA, Chen G, Ding M, Wang S, Shi X, Ke Z, Luo J - Mol. Cancer (2010)

Bottom Line: C3G decreased ethanol-mediated cell adhesion to the extracellular matrix (ECM) as well as the amount of focal adhesions and the formation of lamellipodial protrusion.It inhibited ethanol-stimulated phosphorylation of ErbB2, cSrc, FAK and p130(Cas), as well as interactions among these proteins.C3G may be beneficial in preventing/reducing ethanol-induced breast cancer metastasis.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Internal Medicine, University of Kentucky College of Medicine, Lexington, KY 40536, USA.

ABSTRACT

Background: Ethanol is a tumor promoter. Both epidemiological and experimental studies suggest that ethanol may enhance the metastasis of breast cancer cells. We have previously demonstrated that ethanol increased the migration/invasion of breast cancer cells expressing high levels of ErbB2. Amplification of ErbB2 is found in 20-30% of breast cancer patients and is associated with poor prognosis. We sought to identify agents that can prevent or ameliorate ethanol-induced invasion of breast cancer cells. Cyanidin-3-glucoside (C3G), an anthocyanin present in many vegetables and fruits, is a potent natural antioxidant. Ethanol exposure causes the accumulation of intracellular reactive oxygen species (ROS). This study evaluated the effect of C3G on ethanol-induced breast cancer cell migration/invasion.

Results: C3G attenuated ethanol-induced migration/invasion of breast cancer cells expressing high levels of ErbB2 (BT474, MDA-MB231 and MCF7(ErbB2)) in a concentration dependent manner. C3G decreased ethanol-mediated cell adhesion to the extracellular matrix (ECM) as well as the amount of focal adhesions and the formation of lamellipodial protrusion. It inhibited ethanol-stimulated phosphorylation of ErbB2, cSrc, FAK and p130(Cas), as well as interactions among these proteins. C3G abolished ethanol-mediated p130(Cas)/JNK interaction.

Conclusions: C3G blocks ethanol-induced activation of the ErbB2/cSrc/FAK pathway which is necessary for cell migration/invasion. C3G may be beneficial in preventing/reducing ethanol-induced breast cancer metastasis.

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Effects of C3G on ethanol-induced activation of JNKs. MCF7ErbB2 cells were treated with ethanol (0 or 400 mg/dl) with/without C3G (10, 20 or 40 μM) for 48 h. Cells were seeded on fibronectin-coated culture wells for 3 h. A: Cell lysates were collected and analyzed for the phosphorylation/expression of JNKs with immunoblotting. B: Cell lysates were IP with an anti-JNK antibody and IB with either an anti-p130Cas or anti-JNK antibody. The experiment was replicated three times. C and D: The phoshorylation of JNKs and the association between JNKs and p130Cas were quantified by densitometry. * denotes a statistically significant difference from untreated controls. # denotes a significant difference from ethanol-treated groups. ε denotes a significant difference from ethanol- and C3G (10 μM)-treated groups. δ denotes a significant difference from ethanol- and C3G (20 μM)-treated groups.
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Figure 5: Effects of C3G on ethanol-induced activation of JNKs. MCF7ErbB2 cells were treated with ethanol (0 or 400 mg/dl) with/without C3G (10, 20 or 40 μM) for 48 h. Cells were seeded on fibronectin-coated culture wells for 3 h. A: Cell lysates were collected and analyzed for the phosphorylation/expression of JNKs with immunoblotting. B: Cell lysates were IP with an anti-JNK antibody and IB with either an anti-p130Cas or anti-JNK antibody. The experiment was replicated three times. C and D: The phoshorylation of JNKs and the association between JNKs and p130Cas were quantified by densitometry. * denotes a statistically significant difference from untreated controls. # denotes a significant difference from ethanol-treated groups. ε denotes a significant difference from ethanol- and C3G (10 μM)-treated groups. δ denotes a significant difference from ethanol- and C3G (20 μM)-treated groups.

Mentions: c-Jun N-terminal kinases (JNKs), a member of mitogen-activated protein kinases (MAPKs), regulate cell migration/invasion [28]. We have previously demonstrated that JNKs are essential for ethanol-mediated cell invasion/migration [10]. JNK activation is regulated by p130Cas [27]. C3G inhibited ethanol-induced JNK phosphorylation and p130Cas/JNK association in MCF7ErbB2 cells (Figure 5).


Cyanidin-3-glucoside inhibits ethanol-induced invasion of breast cancer cells overexpressing ErbB2.

Xu M, Bower KA, Wang S, Frank JA, Chen G, Ding M, Wang S, Shi X, Ke Z, Luo J - Mol. Cancer (2010)

Effects of C3G on ethanol-induced activation of JNKs. MCF7ErbB2 cells were treated with ethanol (0 or 400 mg/dl) with/without C3G (10, 20 or 40 μM) for 48 h. Cells were seeded on fibronectin-coated culture wells for 3 h. A: Cell lysates were collected and analyzed for the phosphorylation/expression of JNKs with immunoblotting. B: Cell lysates were IP with an anti-JNK antibody and IB with either an anti-p130Cas or anti-JNK antibody. The experiment was replicated three times. C and D: The phoshorylation of JNKs and the association between JNKs and p130Cas were quantified by densitometry. * denotes a statistically significant difference from untreated controls. # denotes a significant difference from ethanol-treated groups. ε denotes a significant difference from ethanol- and C3G (10 μM)-treated groups. δ denotes a significant difference from ethanol- and C3G (20 μM)-treated groups.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2984473&req=5

Figure 5: Effects of C3G on ethanol-induced activation of JNKs. MCF7ErbB2 cells were treated with ethanol (0 or 400 mg/dl) with/without C3G (10, 20 or 40 μM) for 48 h. Cells were seeded on fibronectin-coated culture wells for 3 h. A: Cell lysates were collected and analyzed for the phosphorylation/expression of JNKs with immunoblotting. B: Cell lysates were IP with an anti-JNK antibody and IB with either an anti-p130Cas or anti-JNK antibody. The experiment was replicated three times. C and D: The phoshorylation of JNKs and the association between JNKs and p130Cas were quantified by densitometry. * denotes a statistically significant difference from untreated controls. # denotes a significant difference from ethanol-treated groups. ε denotes a significant difference from ethanol- and C3G (10 μM)-treated groups. δ denotes a significant difference from ethanol- and C3G (20 μM)-treated groups.
Mentions: c-Jun N-terminal kinases (JNKs), a member of mitogen-activated protein kinases (MAPKs), regulate cell migration/invasion [28]. We have previously demonstrated that JNKs are essential for ethanol-mediated cell invasion/migration [10]. JNK activation is regulated by p130Cas [27]. C3G inhibited ethanol-induced JNK phosphorylation and p130Cas/JNK association in MCF7ErbB2 cells (Figure 5).

Bottom Line: C3G decreased ethanol-mediated cell adhesion to the extracellular matrix (ECM) as well as the amount of focal adhesions and the formation of lamellipodial protrusion.It inhibited ethanol-stimulated phosphorylation of ErbB2, cSrc, FAK and p130(Cas), as well as interactions among these proteins.C3G may be beneficial in preventing/reducing ethanol-induced breast cancer metastasis.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Internal Medicine, University of Kentucky College of Medicine, Lexington, KY 40536, USA.

ABSTRACT

Background: Ethanol is a tumor promoter. Both epidemiological and experimental studies suggest that ethanol may enhance the metastasis of breast cancer cells. We have previously demonstrated that ethanol increased the migration/invasion of breast cancer cells expressing high levels of ErbB2. Amplification of ErbB2 is found in 20-30% of breast cancer patients and is associated with poor prognosis. We sought to identify agents that can prevent or ameliorate ethanol-induced invasion of breast cancer cells. Cyanidin-3-glucoside (C3G), an anthocyanin present in many vegetables and fruits, is a potent natural antioxidant. Ethanol exposure causes the accumulation of intracellular reactive oxygen species (ROS). This study evaluated the effect of C3G on ethanol-induced breast cancer cell migration/invasion.

Results: C3G attenuated ethanol-induced migration/invasion of breast cancer cells expressing high levels of ErbB2 (BT474, MDA-MB231 and MCF7(ErbB2)) in a concentration dependent manner. C3G decreased ethanol-mediated cell adhesion to the extracellular matrix (ECM) as well as the amount of focal adhesions and the formation of lamellipodial protrusion. It inhibited ethanol-stimulated phosphorylation of ErbB2, cSrc, FAK and p130(Cas), as well as interactions among these proteins. C3G abolished ethanol-mediated p130(Cas)/JNK interaction.

Conclusions: C3G blocks ethanol-induced activation of the ErbB2/cSrc/FAK pathway which is necessary for cell migration/invasion. C3G may be beneficial in preventing/reducing ethanol-induced breast cancer metastasis.

Show MeSH
Related in: MedlinePlus