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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

ROS production in MDA-MB231 cells treated with AEs. (a) The presence of ROS was detected by DHE fluorescent staining after 10 days treatment. Scale bar: 50 μm, original magnification 20x. (b) Red fluorescent-stained cells versus total cells were counted using an inverted fluorescence microscope. The results are the mean ± SD of at least three independent experiments. Significant statistical differences are indicated by asterisks: ∗∗p = 0.0012. (c) NAC reduced the antiproliferative effect of AEs (30 μM for 10 days). The results are the mean ± SD of at least three independent experiments. Significant statistical differences are indicated by asterisks: ∗∗p = 0.0012.
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fig6: ROS production in MDA-MB231 cells treated with AEs. (a) The presence of ROS was detected by DHE fluorescent staining after 10 days treatment. Scale bar: 50 μm, original magnification 20x. (b) Red fluorescent-stained cells versus total cells were counted using an inverted fluorescence microscope. The results are the mean ± SD of at least three independent experiments. Significant statistical differences are indicated by asterisks: ∗∗p = 0.0012. (c) NAC reduced the antiproliferative effect of AEs (30 μM for 10 days). The results are the mean ± SD of at least three independent experiments. Significant statistical differences are indicated by asterisks: ∗∗p = 0.0012.

Mentions: Since reactive oxygen species (ROS) are well-known inducers of cellular senescence, we tested whether AEs increase oxidative stress in breast cancer cells. To accomplish this, cells were incubated with DHE which is an indicator of the presence of superoxide anion, key radical in ROS generation. As shown in Figures 6(a) and 6(b) AEs-treated cells, according to the increased number of bright red fluorescent cells, showed enhanced level of superoxide anions compared to control 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)

ROS production in MDA-MB231 cells treated with AEs. (a) The presence of ROS was detected by DHE fluorescent staining after 10 days treatment. Scale bar: 50 μm, original magnification 20x. (b) Red fluorescent-stained cells versus total cells were counted using an inverted fluorescence microscope. The results are the mean ± SD of at least three independent experiments. Significant statistical differences are indicated by asterisks: ∗∗p = 0.0012. (c) NAC reduced the antiproliferative effect of AEs (30 μM for 10 days). The results are the mean ± SD of at least three independent experiments. Significant statistical differences are indicated by asterisks: ∗∗p = 0.0012.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig6: ROS production in MDA-MB231 cells treated with AEs. (a) The presence of ROS was detected by DHE fluorescent staining after 10 days treatment. Scale bar: 50 μm, original magnification 20x. (b) Red fluorescent-stained cells versus total cells were counted using an inverted fluorescence microscope. The results are the mean ± SD of at least three independent experiments. Significant statistical differences are indicated by asterisks: ∗∗p = 0.0012. (c) NAC reduced the antiproliferative effect of AEs (30 μM for 10 days). The results are the mean ± SD of at least three independent experiments. Significant statistical differences are indicated by asterisks: ∗∗p = 0.0012.
Mentions: Since reactive oxygen species (ROS) are well-known inducers of cellular senescence, we tested whether AEs increase oxidative stress in breast cancer cells. To accomplish this, cells were incubated with DHE which is an indicator of the presence of superoxide anion, key radical in ROS generation. As shown in Figures 6(a) and 6(b) AEs-treated cells, according to the increased number of bright red fluorescent cells, showed enhanced level of superoxide anions compared to control 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