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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

Effect of AEs on lysine acetylation of total proteins in MDA-MB231 cells. Cells were treated with low doses of AEs for 10 days. Cell lysates were analyzed for lysine acetylation of total proteins. Immunoblot is representative of at least three experiments. The intensities of electrophoretic bands relative to the immunoblot shown were quantified by densitometry.
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fig5: Effect of AEs on lysine acetylation of total proteins in MDA-MB231 cells. Cells were treated with low doses of AEs for 10 days. Cell lysates were analyzed for lysine acetylation of total proteins. Immunoblot is representative of at least three experiments. The intensities of electrophoretic bands relative to the immunoblot shown were quantified by densitometry.

Mentions: Protein acetylation of lysine residues is an important reversible modification controlling cellular protein expression [48]. We investigated the effect of AEs treatment on acetylation of total proteins in breast cancer cells. MDA-MB231 cells were cultured for 24 h before adding either the vehicle or various concentrations of AEs (10 and 30 μM) for 10 days and then harvested. As shown in Figure 5, the level of protein acetylation is markedly increased in treated cells as indicated by reported densitometric values. These results provide evidence that long term exposure to low concentrations of AEs is associated with increased level of lysines acetylation of total proteins.


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)

Effect of AEs on lysine acetylation of total proteins in MDA-MB231 cells. Cells were treated with low doses of AEs for 10 days. Cell lysates were analyzed for lysine acetylation of total proteins. Immunoblot is representative of at least three experiments. The intensities of electrophoretic bands relative to the immunoblot shown were quantified by densitometry.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig5: Effect of AEs on lysine acetylation of total proteins in MDA-MB231 cells. Cells were treated with low doses of AEs for 10 days. Cell lysates were analyzed for lysine acetylation of total proteins. Immunoblot is representative of at least three experiments. The intensities of electrophoretic bands relative to the immunoblot shown were quantified by densitometry.
Mentions: Protein acetylation of lysine residues is an important reversible modification controlling cellular protein expression [48]. We investigated the effect of AEs treatment on acetylation of total proteins in breast cancer cells. MDA-MB231 cells were cultured for 24 h before adding either the vehicle or various concentrations of AEs (10 and 30 μM) for 10 days and then harvested. As shown in Figure 5, the level of protein acetylation is markedly increased in treated cells as indicated by reported densitometric values. These results provide evidence that long term exposure to low concentrations of AEs is associated with increased level of lysines acetylation of total proteins.

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