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Artichoke polyphenols induce apoptosis and decrease the invasive potential of the human breast cancer cell line
Anna Maria Mileo1, Donato Di Venere, Vito Linsalata
1Department of Development of Therapeutic Programs, Regina Elena National Cancer Institute, Rome, Italy.
Abstract:
The human breast cancer cell line, estrogen receptor negative, MDA-MB231, was used to evaluate the antitumor effect of polyphenolic extracts from the edible part of artichokes (AEs). Treatment of cancer cells reduced cell viability and inhibited cell growth in a dose-dependent manner. Importantly, AEs did not have any effect on normal breast epithelial cell line, MCF10A. Chlorogenic acid (ChA), the most representative component of the polyphenolic fraction of artichoke, had no prominent effects on the cell death rate of MDA-MB231 cells. The addition of AEs to the cells, rather than ChA, triggered apoptosis via a mitochondrial and a death-receptor pathway, as shown by the activation of caspase-9 and caspase-8, respectively. Furthermore, an increase of the Bax:Bcl2 ratio and up-regulation of cyclin-dependent kinase inhibitor, p21(WAF1), crucial apoptotic players, were documented. According to our data on activation of caspase-9, a loss of mitochondrial transmembrane potential (Ψ(m)) was shown. Cell motility and invasion capabilities were remarkably inhibited by AEs-treatment in highly invasive MDA-MB231 cells. In addition, a significant decrease of proteolytic activity of metalloproteinase-2 protein (MMP-2), involved in degrading components of the extracellular matrix, was detected. Our findings indicate that AEs reduced cell viability, inhibited cell growth, triggered apoptotic mechanisms, and showed inhibitory properties against the invasive behavior of MDA-MB231 cancer cell line. Altogether, these data indicate the potential chemopreventive activity of artichoke polyphenolic extracts.
Insights
Artichoke extracts (AEs) show antitumor effects against estrogen receptor-negative breast cancer cells by inducing apoptosis and inhibiting growth. AEs demonstrated potential chemopreventive activity without harming normal cells.
Area of Science:
- Oncology
- Pharmacology
- Natural Products
Background:
- Estrogen receptor-negative breast cancer, such as the MDA-MB231 cell line, presents a significant therapeutic challenge.
- Polyphenolic compounds from edible plants are increasingly investigated for their potential health benefits and anticancer properties.
Purpose of the Study:
- To investigate the antitumor effects of artichoke (Cynara scolymus) polyphenol extracts (AEs) on the MDA-MB231 human breast cancer cell line.
- To determine if AEs induce apoptosis and inhibit the invasive potential of these cancer cells.
- To compare the effects of AEs with its main component, chlorogenic acid (ChA).
Main Methods:
- Treatment of MDA-MB231 and MCF10A cells with varying concentrations of AEs and ChA.
- Assessment of cell viability, proliferation, apoptosis (caspase activation, Bax:Bcl2 ratio, p21(WAF1) expression, mitochondrial potential), cell motility, invasion, and matrix metalloproteinase-2 (MMP-2) activity.
- Utilized Western blotting, flow cytometry, and other biochemical assays.
Main Results:
- AEs significantly reduced MDA-MB231 cell viability and inhibited proliferation in a dose-dependent manner.
- AEs induced apoptosis through both mitochondrial (caspase-9 activation, loss of mitochondrial potential) and death-receptor (caspase-8 activation) pathways, with increased Bax:Bcl2 ratio and p21(WAF1) expression.
- AEs markedly inhibited cell motility, invasion, and MMP-2 activity in MDA-MB231 cells, while showing no toxicity to normal MCF10A cells. Chlorogenic acid alone had minimal impact.
Conclusions:
- Artichoke polyphenol extracts possess significant antitumor properties against estrogen receptor-negative breast cancer cells.
- AEs effectively induce apoptosis and suppress the invasive phenotype of MDA-MB231 cells.
- These findings suggest that artichoke extracts have potential as a chemopreventive agent against breast cancer.
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