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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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Related in: MedlinePlus

Effects of C3G on ethanol-mediated adhesion of breast cancer cells. MCF7ErbB2 cells were treated with ethanol (0, 200 or 400 mg/dl) with/without C3G (10, 20 or 40 μM) for 48 h, and then equal amounts of cells were seeded on fibronectin-coated culture wells, allowing attachment for 1 h. The number of adherent cells was determined as described under the Materials and Methods and presented relative to untreated controls. Each datum point was the mean ± SEM of three independent experiments. * denotes a statistically significant difference from untreated controls. # denotes a significant difference from ethanol-treated groups.
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Figure 2: Effects of C3G on ethanol-mediated adhesion of breast cancer cells. MCF7ErbB2 cells were treated with ethanol (0, 200 or 400 mg/dl) with/without C3G (10, 20 or 40 μM) for 48 h, and then equal amounts of cells were seeded on fibronectin-coated culture wells, allowing attachment for 1 h. The number of adherent cells was determined as described under the Materials and Methods and presented relative to untreated controls. Each datum point was the mean ± SEM of three independent experiments. * denotes a statistically significant difference from untreated controls. # denotes a significant difference from ethanol-treated groups.

Mentions: The adhesion of cancer cells to ECM or cell/ECM interaction is an important step of metastasis. We have previously demonstrated that ethanol enhances the adhesion of breast cancer cells to fibronectin, an essential protein in the ECM [19]. Ethanol did not affect the attachment of breast cancer cells to poly-lysine (data not shown). We examined the effect of C3G on ethanol-mediated cell adhesion to fibronectin. MCF7ErbB2 cells were pretreated with ethanol with/without C3G for 48 hours, then the cells were seeded on fibronectin precoated plates and allowed to attach for 1 hour in the presence/absence of ethanol and/or C3G. As shown in Figure 2, ethanol increased the adhesion of MCF7ErbB2 cells to fibronectin and C3G significantly inhibited ethanol-enhanced adhesion in a concentration-dependent manner. C3G alone (10-20 μM) did not affect cell adhesion (data not shown). C3G similarly inhibited ethanol-induced adhesion of MDA-MB231 cells to the ECM (data not shown).


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-mediated adhesion of breast cancer cells. MCF7ErbB2 cells were treated with ethanol (0, 200 or 400 mg/dl) with/without C3G (10, 20 or 40 μM) for 48 h, and then equal amounts of cells were seeded on fibronectin-coated culture wells, allowing attachment for 1 h. The number of adherent cells was determined as described under the Materials and Methods and presented relative to untreated controls. Each datum point was the mean ± SEM of three independent experiments. * denotes a statistically significant difference from untreated controls. # denotes a significant difference from ethanol-treated groups.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Effects of C3G on ethanol-mediated adhesion of breast cancer cells. MCF7ErbB2 cells were treated with ethanol (0, 200 or 400 mg/dl) with/without C3G (10, 20 or 40 μM) for 48 h, and then equal amounts of cells were seeded on fibronectin-coated culture wells, allowing attachment for 1 h. The number of adherent cells was determined as described under the Materials and Methods and presented relative to untreated controls. Each datum point was the mean ± SEM of three independent experiments. * denotes a statistically significant difference from untreated controls. # denotes a significant difference from ethanol-treated groups.
Mentions: The adhesion of cancer cells to ECM or cell/ECM interaction is an important step of metastasis. We have previously demonstrated that ethanol enhances the adhesion of breast cancer cells to fibronectin, an essential protein in the ECM [19]. Ethanol did not affect the attachment of breast cancer cells to poly-lysine (data not shown). We examined the effect of C3G on ethanol-mediated cell adhesion to fibronectin. MCF7ErbB2 cells were pretreated with ethanol with/without C3G for 48 hours, then the cells were seeded on fibronectin precoated plates and allowed to attach for 1 hour in the presence/absence of ethanol and/or C3G. As shown in Figure 2, ethanol increased the adhesion of MCF7ErbB2 cells to fibronectin and C3G significantly inhibited ethanol-enhanced adhesion in a concentration-dependent manner. C3G alone (10-20 μM) did not affect cell adhesion (data not shown). C3G similarly inhibited ethanol-induced adhesion of MDA-MB231 cells to the ECM (data not shown).

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