Pro-oxidant and pro-apoptotic activity of polyphenol extract from Annurca apple and its underlying mechanisms in human breast cancer cells

  • Authors:
    • Stefania D'Angelo
    • Elisa Martino
    • Concetta Paola Ilisso
    • Maria Libera Bagarolo
    • Marina Porcelli
    • Giovanna Cacciapuoti
  • View Affiliations

  • Published online on: July 31, 2017     https://doi.org/10.3892/ijo.2017.4088
  • Pages: 939-948
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Among nutraceuticals, polyphenols represent the most intriguing and studied class of compounds that can be therapeutics for a large spectrum of the most common diseases, including cancer. Although polyphenols are well known as potent antioxidants, a pro-oxidant effect has been associated with a pro-apoptotic function of these compounds in various types of tumor cells. Annurca apple, a southern Italian variety, is characterized by an extremely high content of polyphenols and displays a stronger antioxidant activity compared with other varieties. In the present study we explored the antiproliferative effect of Annurca apple polyphenol extract (APE) in human breast cancer MCF-7 cells and we investigated the underlying mechanisms. Results showed that at 500 µM catechin equivalent (EqC) APE acts as a pro-oxidant increasing thiobarbituric acid-reactive species cell content of approximately 6-fold more than the untreated cells. We found that APE strongly inhibits the proliferation of MCF-7 cells by inducing G2/M cell cycle arrest and apoptosis. Immunoblot analysis demonstrated that APE treatment increases the levels of p53 and p21, downregulates the expression of the cell cycle regulatory protein cyclin D1, and inhibits ERK1/2 phosphorylation. Moreover, APE treatment caused a marked increase of pro-apoptotic Bax/Bcl-2 ratio paralleled by caspase-9, -6, -7, and poly(ADP ribose) polymerase cleavage. Altogether our data indicate that APE, at elevated concentrations, acts as a potent pro-oxidant and antiproliferative agent able to downregulate ERK1/2 pathway leading to cell cycle inhibition and apoptosis and provides a rationale for its potential use in the development of novel therapeutics towards breast cancer.
View Figures
View References

Related Articles

Journal Cover

September 2017
Volume 51 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
APA
D'Angelo, S., Martino, E., Ilisso, C.P., Bagarolo, M.L., Porcelli, M., & Cacciapuoti, G. (2017). Pro-oxidant and pro-apoptotic activity of polyphenol extract from Annurca apple and its underlying mechanisms in human breast cancer cells. International Journal of Oncology, 51, 939-948. https://doi.org/10.3892/ijo.2017.4088
MLA
D'Angelo, S., Martino, E., Ilisso, C. P., Bagarolo, M. L., Porcelli, M., Cacciapuoti, G."Pro-oxidant and pro-apoptotic activity of polyphenol extract from Annurca apple and its underlying mechanisms in human breast cancer cells". International Journal of Oncology 51.3 (2017): 939-948.
Chicago
D'Angelo, S., Martino, E., Ilisso, C. P., Bagarolo, M. L., Porcelli, M., Cacciapuoti, G."Pro-oxidant and pro-apoptotic activity of polyphenol extract from Annurca apple and its underlying mechanisms in human breast cancer cells". International Journal of Oncology 51, no. 3 (2017): 939-948. https://doi.org/10.3892/ijo.2017.4088