Effects of Annurca Apple (Malus pumila cv Annurca) Polyphenols on Breast Cancer Cells

Author(s): Stefania D'Angelo*, Elisa Martino, Giovanna Cacciapuoti.

Journal Name: Current Nutrition & Food Science

Volume 15 , Issue 7 , 2019

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Abstract:

Background: Dietary micronutrients have been proposed as effective inhibitory agents for cancer initiation, progression, and incidence. Among them, polyphenols, present in different foods and beverages, have retained attention in recent years. Apples are among the most consumed fruits worldwide, and several studies suggest that apple polyphenols could play a role in the prevention of degenerative diseases.

Aims and Objectives: The present study aimed at evaluating the effects of Annurca flesh polyphenols extract (AFPE) effects of proliferation on MCF-7 cells.

Methods: The data indicated that apple polyphenolic compounds had a significant antiproliferative action on MCF-7 cells and 500μM EqC AFPE induced a cell cycle arrest at G2/M. AFPE was also capable of inducing morphological changes as evidenced by nuclear condensation.

Results: The cellular, morphological, and molecular data unequivocally suggested that induction of cellular apoptosis was mainly responsible for the previously observed antiproliferation-induced AFPE on MCF-7 cells.

Conclusion: Taken together, AFPE that acts at a low micromolar range against breast cancer cells may be considered as a promising candidate for anticancer therapy.

Keywords: Annurca apple, apoptosis, breast cancer, dietary micronutrients, MCF-7, polyphenol.

[1]
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J Clin 2017; 67: 7-30.
[2]
Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin 2015; 65: 87-108.
[3]
Sauter ER. Breast cancer prevention: current approaches and future directions. Eur J Breast Health 2018; 14(2): 64-71.
[4]
WHO. Breast Cancer. (Accessed: December 12, 2017). Available from: http://www.who.int/cancer/prevention/diagnosis-screening/ breast-cancer/en/
[5]
WCRF World Cancer Research Fund International. Continuous Update Project (Cup) (Accessed on 20 July 2017). http://www. wcrf.org/int/research-we-fund/continuous-update-project-cup
[6]
Milner JA. Molecular targets for bioactive food components. J Nutr 2004; 134: 2492s-8s.
[7]
Motti ML, D’Angelo S, Meccariello R. MicroRNAs, cancer and diet: Facts and new exciting perspectives. Curr Mol Pharmacol 2018; 11: 90-6.
[8]
Gerhauser C. Cancer chemopreventive potential of apples, apple juice, and apple components. Planta Med 2008; 74(13): 1608-24.
[9]
Thompson R. Preventing cancer: The role of food, nutrition and physical activity. J Fam Health Care 2010; 20(3): 100-2.
[10]
Dandamudi A, Tommie J, Nommsen-Rivers L, Couch S. Dietary patterns and breast cancer risk: A systematic review. Anticancer Res 2018; 38(6): 3209-22.
[11]
Braakhuis AJ, Campion P, Bishop K. Reducing breast cancer recurrence: The role of dietary polyphenolics. Nutrients 2016; 8(9)E547
[12]
Anantharaju PG, Gowda PC, Vimalambike MG, Madhunapantula SV. An overview on the role of dietary phenolics for the treatment of cancers. Nutr J 2016; 15: 99.
[13]
Pérez-Jiménez J, Neveu V, Vos F, Scalbert A. Identification of the 100 richest dietary sources of polyphenols: an application of the Phenol-Explorer database. Eur J Clin Nutr 2010; 64: S112-20.
[14]
Pandey KB, Rizvi SI. Plant polyphenols as dietary antioxidants in human health and disease. Oxid Med Cell Longev 2009; 2(5): 270-8.
[15]
Hyson DA. A comprehensive review of apples and apple components and their relationship to human health. Adv Nutr 2011; 2: 408-20.
[16]
Schiavano GF, De Santi M, Brandi G, et al. Inhibition of breast cancer cell proliferation and in vitro tumorigenesis by a new red apple cultivar. PLoS One 2015; 10(8)e0135840
[17]
Jedrychowski W, Maugeri U, Popiela T, et al. Case-control study on beneficial effect of regular consumption of apples on colorectal cancer risk in a population with relatively low intake of fruits and vegetables. Eur J Cancer Prev 2010; 19: 42-7.
[18]
Francini A, Sebastiani L. Phenolic compounds in apple (Malus x domestica Borkh): Compounds characterization and stability during postharvest and after processing. Antioxidants 2013; 2: 181-93.
[19]
Rana S, Bhushan S. Apple phenolics as nutraceuticals: Assessment, analysis and application. J Food Sci Technol 2016; 53: 1727-38.
[20]
Hyson DA. Comprehensive review of apple and apple compounds and their relationship to human health. Adv Nutr 2011; 2: 408-20.
[21]
Tu SH, Chen LC, Ho YS. An apple a day to prevent cancer formation: Reducing cancer risk with flavonoids. J Food Drug Anal 2017; 25: 119-24.
[22]
Kern M, Tjaden Z, Ngiewih Y, et al. Inhibitors of the epidermal growth factor receptor in apple juice extract. Mol Nutr Food Res 2005; 49: 317-28.
[23]
Sun J, Chu YF, Wu X, Liu RH. Antioxidant and antiproliferative activities of common fruits. J Agric Food Chem 2002; 50: 7449-54.
[24]
Tow WW, Premier R, Jing H, Ajlouni S. Antioxidant and antiproliferation effects of extractable and nonextractable polyphenols isolated from apple waste using different extraction methods. J Food Sci 2011; 76: T163-72.
[25]
Lo Scalzo R, Testoni A, Genna A. “Annurca” apple fruit, a southern Italy apple cultivar: Textural properties and aroma composition. Food Chem 2001; 73: 333-43.
[26]
D’Angelo S, Cimmino A, Raimo M, Salvatore A, Zappia V, Galletti P. Effect of reddening-ripening on the antioxidant activity of polyphenol extracts from cv. ‘Annurca’ apple fruits. J Agric Food Chem 2007; 55: 9977-85.
[27]
Napolitano A, Cascone A, Graziani G, et al. Influence of variety and storage on the polyphenol composition of apple flesh. J Agric Food Chem 2004; 52: 6526-31.
[28]
D’Angelo S, Sammartino D. Protective effect of Annurca apple extract against oxidative damage in human erythrocytes. Curr Nutr Food Sci 2015; 11: 248-56.
[29]
Graziani G, D’Argenio G, Tuccillo C, et al. Apple polyphenol extracts prevent damage to human gastric epithelial cells in vitro and to rat gastric mucosa in vivo. Gut 2005; 54: 193-200.
[30]
Fini L, Piazzi G, Daoud Y, et al. Chemoprevention of intestinal polyps in ApcMin/+ mice fed with western or balanced diets by drinking Annurca apple polyphenol extract. Cancer Prev Res 2011; 4: 907-15.
[31]
D’Angelo S, La Porta R, Napolitano M, Galletti P, Quagliuolo L, Boccellino M. Effect of Annurca apple polyphenols on human HaCaT keratinocytes proliferation. J Med Food 2012; 15: 1024-31.
[32]
D’Angelo S, Martino E, Ilisso CP, Bagarolo ML, 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. Int J Oncol 2017; 51: 939-48.
[33]
Singleton VL, Orthofer R, Lamuela-Raventos RM. Analysis of total phenols and other oxidation substrates and antioxidants by means of Folin-Ciocalteu reagent. Methods Enzymol 1999; 299: 152-78.
[34]
D’Angelo S, Ingrosso D, Migliardi V, et al. Hydroxytyrosol, a natural antioxidant from olive oil, prevents protein damage induced by long-wave ultraviolet radiation in melanoma cells. Free Radic Biol Med 2005; 38: 908-19.
[35]
Fantini M, Benvenuto M, Masuelli L, et al. In vitro and in vivo antitumoral effects of combinations of polyphenols, or polyphenols and anticancer drugs: perspectives on cancer treatment. Int J Mol Sci 2015; 16: 9236-82.
[36]
Niedzwiecki A, Roomi MW, Kalinovsky T, Rath M. Anticancer efficacy of polyphenols and their combinations Nutrients 2016; 9; 8(9): E552
[37]
Curti V, Di Lorenzo A, Dacrema M, Xiao J, Nabavi SM, Daglia M. In vitro polyphenol effects on apoptosis: An update of literature data. Semin Cancer Biol 2017; 46: 119-31.
[38]
Lecumberri E, Dupertuis YM, Miralbell R, Pichard C. Green tea polyphenol epigallocatechin-3-gallate (EGCG) as adjuvant in cancer therapy. Clin Nutr 2013; 32(6): 894-903.
[39]
Shamshoum H, Vlavcheski F, Tsiani E. Anticancer effects of oleuropein. Biofactors 2017; 43(4): 517-28.
[40]
Budisan L, Gulei D, Zanoaga OM, et al. Dietary intervention by phytochemicals and their role in modulating coding and non-coding genes in cancer. Int J Mol Sci 2017; 18(6)E117
[41]
Moore J, Yousef M, Tsiani E. Anticancer effects of rosemary (Rosmarinus officinalis L.) Extract and rosemary extract polyphenols. Nutrients 2016; 8(11)E731
[42]
Dong S, Inoue A, Zhu Y, Tanji M, Kiyama R. Activation of rapid signaling pathways and the subsequent transcriptional regulation for the proliferation of breast cancer MCF-7 cells by the treatment with an extract of Glycyrrhiza glabra root. Food Chem Toxicol 2007; 45(12): 2470-8.
[43]
Tang EL, Rajarajeswaran J, Fung SY, Kanthimathi MS. Antioxidant activity of Coriandrum sativum and protection against DNA damage and cancer cell migration. BMC Complement Altern Med 2013; 9: 347.
[44]
Namvar F, Mohamad R, Baharara J, Zafar-Balanejad S, Fargahi F, Rahman HS. Antioxidant, antiproliferative, and antiangiogenesis effects of polyphenol-rich seaweed (Sargassum muticum). Biomed Res Int 2013; 2013604787
[45]
Chen X, Li Y, Lin Q, et al. Tea polyphenols induced apoptosis of breast cancer cells by suppressing the expression of Survivin. Sci Rep 2014; 4: 4416.
[46]
Bravo L. Polyphenols: Chemistry, dietary, sources, metabolism and nutritional significance. Nutr Rev 1998; 56(1): 317-33.
[47]
Manach C, Scalbert A, Morand C, Rémésy C, Jiménez L. Polyphenols: Food sources and bioavailability. Am J Clin Nutr 2004; 79: 727-47.
[48]
Martino E, Vuoso DC, D’Angelo S, et al. Annurca apple polyphenol extract selectively kills MDA-MB-231 cells through ROS generation, sustained JNK activation and cell growth and survival inhibition. Sci Rep 2019; 9(1): 13045.


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Article Details

VOLUME: 15
ISSUE: 7
Year: 2019
Page: [745 - 751]
Pages: 7
DOI: 10.2174/1573401315666190206142025
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