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Long Term Exposure to Polyphenols of Artichoke (Cynara scolymus L.) Exerts Induction of Senescence Driven Growth Arrest in the MDA-MB231 Human Breast Cancer Cell Line.

Mileo AM, Di Venere D, Abbruzzese C, Miccadei S - Oxid Med Cell Longev (2015)

Bottom Line: Furthermore, AEs exposure induces a significant increase of senescence-associated β-galactosidase (SA-β-gal) staining and upregulation of tumour suppressor genes, p16(INK4a) and p21(Cip1/Waf1) in MDA-MB231 cells.Inhibition of ROS generation by N-acetylcysteine (NAC) attenuates the antiproliferative effect.Our results suggest that artichoke polyphenols could be a promising dietary tool either in cancer chemoprevention or/and in cancer treatment as a nonconventional, adjuvant therapy.

View Article: PubMed Central - PubMed

Affiliation: Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy.

ABSTRACT
Polyphenolic extracts from the edible part of artichoke (Cynara scolymus L.) have been shown to be potential chemopreventive and anticancer dietary compounds. High doses of polyphenolic extracts (AEs) induce apoptosis and decrease the invasive potential of the human breast cancer cell line, MDA-MB231. However, the molecular mechanism underlying AEs antiproliferative effects is not completely understood. We demonstrate that chronic and low doses of AEs treatment at sublethal concentrations suppress human breast cancer cell growth via a caspases-independent mechanism. Furthermore, AEs exposure induces a significant increase of senescence-associated β-galactosidase (SA-β-gal) staining and upregulation of tumour suppressor genes, p16(INK4a) and p21(Cip1/Waf1) in MDA-MB231 cells. AEs treatment leads to epigenetic alterations in cancer cells, modulating DNA hypomethylation and lysine acetylation levels in total proteins. Cell growth arrest correlates with increased reactive oxygen species (ROS) production in AEs treated breast cancer cells. Inhibition of ROS generation by N-acetylcysteine (NAC) attenuates the antiproliferative effect. These findings demonstrate that chronic AEs treatment inhibits breast cancer cell growth via the induction of premature senescence through epigenetic and ROS-mediated mechanisms. Our results suggest that artichoke polyphenols could be a promising dietary tool either in cancer chemoprevention or/and in cancer treatment as a nonconventional, adjuvant therapy.

No MeSH data available.


Related in: MedlinePlus

Chronic treatment of AEs induces increased p16INK4a and p21Cip1/Waf1 expression. MDA-MB231 cells were treated with low doses of AEs (10 and 30 μM) for 10 days. Whole cell lysates were tested for (a) p16INK4a and (b) p21Cip1/Waf1 protein expression. Immunoblots are representative of at least three independent experiments. Intensities of electrophoretic bands relative to the immunoblot shown were quantified by densitometry and the values are reported.
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fig3: Chronic treatment of AEs induces increased p16INK4a and p21Cip1/Waf1 expression. MDA-MB231 cells were treated with low doses of AEs (10 and 30 μM) for 10 days. Whole cell lysates were tested for (a) p16INK4a and (b) p21Cip1/Waf1 protein expression. Immunoblots are representative of at least three independent experiments. Intensities of electrophoretic bands relative to the immunoblot shown were quantified by densitometry and the values are reported.

Mentions: To further investigate this antiproliferative mechanism, we examined the expression levels of p21Cip1/Waf1 and p16INK4a, two pivotal cell cycle regulators involved in cellular senescence [44, 45]. Western blotting data demonstrated that the expression levels of p21Cip1/Waf1 and p16INK4a were significantly increased in a dose-depending manner in AEs-treated cells (Figures 3(a) and 3(b)). Optical density measurements were performed using ImageJ software to obtain quantitative values for the protein expressions. Altogether, these findings suggested that low doses and chronic exposure to AEs induced senescence in MDA-MB231 breast cancer cells.


Long Term Exposure to Polyphenols of Artichoke (Cynara scolymus L.) Exerts Induction of Senescence Driven Growth Arrest in the MDA-MB231 Human Breast Cancer Cell Line.

Mileo AM, Di Venere D, Abbruzzese C, Miccadei S - Oxid Med Cell Longev (2015)

Chronic treatment of AEs induces increased p16INK4a and p21Cip1/Waf1 expression. MDA-MB231 cells were treated with low doses of AEs (10 and 30 μM) for 10 days. Whole cell lysates were tested for (a) p16INK4a and (b) p21Cip1/Waf1 protein expression. Immunoblots are representative of at least three independent experiments. Intensities of electrophoretic bands relative to the immunoblot shown were quantified by densitometry and the values are reported.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4477242&req=5

fig3: Chronic treatment of AEs induces increased p16INK4a and p21Cip1/Waf1 expression. MDA-MB231 cells were treated with low doses of AEs (10 and 30 μM) for 10 days. Whole cell lysates were tested for (a) p16INK4a and (b) p21Cip1/Waf1 protein expression. Immunoblots are representative of at least three independent experiments. Intensities of electrophoretic bands relative to the immunoblot shown were quantified by densitometry and the values are reported.
Mentions: To further investigate this antiproliferative mechanism, we examined the expression levels of p21Cip1/Waf1 and p16INK4a, two pivotal cell cycle regulators involved in cellular senescence [44, 45]. Western blotting data demonstrated that the expression levels of p21Cip1/Waf1 and p16INK4a were significantly increased in a dose-depending manner in AEs-treated cells (Figures 3(a) and 3(b)). Optical density measurements were performed using ImageJ software to obtain quantitative values for the protein expressions. Altogether, these findings suggested that low doses and chronic exposure to AEs induced senescence in MDA-MB231 breast cancer cells.

Bottom Line: Furthermore, AEs exposure induces a significant increase of senescence-associated β-galactosidase (SA-β-gal) staining and upregulation of tumour suppressor genes, p16(INK4a) and p21(Cip1/Waf1) in MDA-MB231 cells.Inhibition of ROS generation by N-acetylcysteine (NAC) attenuates the antiproliferative effect.Our results suggest that artichoke polyphenols could be a promising dietary tool either in cancer chemoprevention or/and in cancer treatment as a nonconventional, adjuvant therapy.

View Article: PubMed Central - PubMed

Affiliation: Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy.

ABSTRACT
Polyphenolic extracts from the edible part of artichoke (Cynara scolymus L.) have been shown to be potential chemopreventive and anticancer dietary compounds. High doses of polyphenolic extracts (AEs) induce apoptosis and decrease the invasive potential of the human breast cancer cell line, MDA-MB231. However, the molecular mechanism underlying AEs antiproliferative effects is not completely understood. We demonstrate that chronic and low doses of AEs treatment at sublethal concentrations suppress human breast cancer cell growth via a caspases-independent mechanism. Furthermore, AEs exposure induces a significant increase of senescence-associated β-galactosidase (SA-β-gal) staining and upregulation of tumour suppressor genes, p16(INK4a) and p21(Cip1/Waf1) in MDA-MB231 cells. AEs treatment leads to epigenetic alterations in cancer cells, modulating DNA hypomethylation and lysine acetylation levels in total proteins. Cell growth arrest correlates with increased reactive oxygen species (ROS) production in AEs treated breast cancer cells. Inhibition of ROS generation by N-acetylcysteine (NAC) attenuates the antiproliferative effect. These findings demonstrate that chronic AEs treatment inhibits breast cancer cell growth via the induction of premature senescence through epigenetic and ROS-mediated mechanisms. Our results suggest that artichoke polyphenols could be a promising dietary tool either in cancer chemoprevention or/and in cancer treatment as a nonconventional, adjuvant therapy.

No MeSH data available.


Related in: MedlinePlus