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Vol. 64 No. 8: Biosynthesis, metabolism and biological activities of natural products from medicinal and food plants

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Flavonoids, bioactive components of propolis, exhibit cytotoxic activity and induce cell cycle arrest and apoptosis in human breast cancer cells MDA-MB-231 and MCF-7 – a comparative study

https://doi.org/10.14715/cmb/2018.64.8.1
Agata Kabała-Dzik
Department of Pathology, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia in Katowice, Ostrogórska 30, 41-200 Sosnowiec, Poland
http://orcid.org/0000-0002-3575-8159
Anna Rzepecka-Stojko
Department of Pharmaceutical Chemistry, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia in Katowice, Jagiellońska 4, 41-200 Sosnowiec, Poland
Robert Kubina
Department of Pathology, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia in Katowice, Ostrogórska 30, 41-200 Sosnowiec, Poland
Marcello Iriti
Department of Agricultural and Environmental Sciences, Faculty of Agricultural and Food Sciences, Milan State University, Via G. Celoria 2 - 20133 Milan, Italy
http://orcid.org/0000-0002-5063-1236
Robert D Wojtyczka
Department and Institute of Microbiology and Virology, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia in Katowice, Jagiellońska 4, 41-200 Sosnowiec, Poland
Ewa Buszman
Department of Pharmaceutical Chemistry, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia in Katowice, Jagiellońska 4, 41-200 Sosnowiec
Jerzy Stojko
Department of Toxicology and Bioanalysis, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia in Katowice, Jagiellońska 4, 41-200 Sosnowiec, Poland

Corresponding Author(s) : Agata Kabała-Dzik

adzik@sum.edu.pl

Cellular and Molecular Biology, Vol. 64 No. 8: Biosynthesis, metabolism and biological activities of natural products from medicinal and food plants

Abstract

Breast cancer is one of the most common causes of mortality in women. Flavonoids, among other compounds, are bioactive constituents of propolis. In this comparative study, we investigated the effects of flavonoids apigenin (API), genistein (GEN), hesperidin (HES), naringin (NAR) and quercetin (QUE) on the proliferation, apoptosis, and cell cycle of two different human cancer cells - MDA-MB-231, estrogen-negative, and MCF-7, estrogen-positive receptor breast carcinoma cells. Many cytotoxic reports of flavonoids were performed by MTT assay. However, it's reported that MTT is reduced in metabolically active cells and yields an insoluble purple formazan, which indicates that obtained cytotoxic results of flavonoids could be inconsistent. Cell viability was measured by NR, neutral red assay, while the percentage of apoptotic cells and cell cycle arrest were determined by flow cytometry and Muse cell cycle assay, respectively. The results showed a high dose-dependent effect in cell viability tests. IC50 values were as follows (MCF-7/MDA-MB-231, for 48 h, in µM): 9.39/50.83 for HES, 25.19/88.17 for API, 40.26/333.51 for NAR, 49.49/47.50 for GEN and 95.12/130.10 for QUE. Flavonoid-induced apoptosis was dose- and time-dependent, for both cancer cell lines, though flavonoids were more active on MCF-7 cells. The flavonoids also induced cell cycle arrest in cancer cells.

Keywords

Flavonoids Propolis Breast cancer.
KabaÅ‚a-Dzik, A., Rzepecka-Stojko, A., Kubina, R., Iriti, M., Wojtyczka, R. D., Buszman, E., & Stojko, J. (2018). Flavonoids, bioactive components of propolis, exhibit cytotoxic activity and induce cell cycle arrest and apoptosis in human breast cancer cells MDA-MB-231 and MCF-7 – a comparative study. Cellular and Molecular Biology, 64(8), 1–10. https://doi.org/10.14715/cmb/2018.64.8.1
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References
  1. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015; 136(5): E359-86.
  2. Cadoo KA, Fornier MN, Morris PG. Biological subtypes of breast cancer: current concepts and implications for recurrence patterns. Q J Nucl Med Mol Imaging. 2013; 57(4): 312-21.
  3. Howland NK, Driver TD, Sedrak MP, Wen X, Dong W, Hatch S et al. Lymph node involvement in immunohistochemistry-based molecular classifications of breast cancer. J Surg Res. 2013; 185(2): 697-703.
  4. Krishnamurthy S, Poornima R, Challa VR, Goud YG. Triple negative breast cancer - our experience and review. Indian J Surg Oncol. 2012; 3(1): 12-6.
  5. Lin NU, Vanderplas A, Hughes ME, Theriault RL, Edge SB, Wong YN et al. Clinicopathologic features, patterns of recurrence, and survival among women with triple-negative breast cancer in the National Comprehensive Cancer Network. Cancer. 2012; 118(22): 5463-72.
  6. Stevens KN, Vachon CM, Couch FJ. Genetic susceptibility to triple-negative breast cancer. Cancer Res. 2013; 73(7): 2025-30.
  7. Montagna E, Maisonneuve P, Rotmensz N, Cancello G, Iorfida M, Balduzzi A et al. Heterogeneity of triple-negative breast cancer: histologic subtyping to inform the outcome. Clin Breast Cancer. 2013; 13(1): 31-9.
  8. Bauer KR, Brown M, Cress RD, Parise CA, Caggiano V. Descriptive analysis of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative invasive breast cancer, the so-called triple-negative phenotype: a population-based study from the California cancer Registry. Cancer. 2007; 109(9): 1721-8.
  9. Bertucci F, Finetti P, Cervera N, Charafe-Jauffret E, Buttarelli M, Jacquemier J et al. How different are luminal A and basal breast cancers? Int J Cancer. 2009; 124(6): 1338-48.
  10. Foulkes WD, Smith IE, Reis-Filho JS. Triple-negative breast cancer. N Engl J Med. 2010; 363(20): 1938-48.
  11. Pal SK, Childs BH, Pegram M. Triple negative breast cancer: unmet medical needs. Breast Cancer Res Treat. 2011; 125(3): 627-36.
  12. Whitman GJ, Albarracin CT, Gonzalez-Angulo AM. Triple-negative breast cancer: what the radiologist needs to know. Semin Roentgenol. 2011; 46(1): 26-39.
  13. Wolff AC, Hammond ME, Hicks DG, Dowsett M, McShane LM, Allison KH et al. Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. Arch Pathol Lab Med. 2014; 138(2): 241-56.
  14. Minami CA, Chung DU, Chang HR. Management options in triple-negative breast cancer. Breast Cancer (Auckl). 2011; 5: 175-99.
  15. O'Toole SA, Beith JM, Millar EK, West R, McLean A, Cazet A et al. Therapeutic targets in triple negative breast cancer. J Clin Pathol. 2013; 66(6): 530-42.
  16. Reddy KB. Triple-negative breast cancers: an updated review on treatment options. Curr Oncol. 2011; 18(4): e173-9.
  17. Santana-Davila R, Perez EA. Treatment options for patients with triple-negative breast cancer. J Hematol Oncol. 2010; 3: 42.
  18. Stockmans G, Deraedt K, Wildiers H, Moerman P, Paridaens R. Triple-negative breast cancer. Curr Opin Oncol. 2008; 20(6): 614-20.
  19. Sporn MB, Suh N. Chemoprevention of cancer. Carcinogenesis. 2000; 21(3): 525-30.
  20. Karikas GA. Anticancer and chemopreventing natural products: some biochemical and therapeutic aspects. J BUON. 2010; 15(4): 627-38.
  21. Marcucci MC, Ferreres F, Garcia-Viguera C, Bankova VS, De Castro SL, Dantas AP et al. Phenolic compounds from Brazilian propolis with pharmacological activities. J Ethnopharmacol. 2001; 74(2): 105-12.
  22. Bankova V, Boudourova-Krasteva G, Sforcin JM, Frete X, Kujumgiev A, Maimoni-Rodella R et al. Phytochemical evidence for the plant origin of Brazilian propolis from Sao Paulo state. Z Naturforsch C. 1999; 54(5-6): 401-5.
  23. Toreti VC, Sato HH, Pastore GM, Park YK. Recent progress of propolis for its biological and chemical compositions and its botanical origin. Evid Based Complement Alternat Med. 2013; 2013: 697390.
  24. Khayyal MT, el-Ghazaly MA, el-Khatib AS. Mechanisms involved in the antiinflammatory effect of propolis extract. Drugs Exp Clin Res. 1993; 19(5): 197-203.
  25. Kujumgiev A, Tsvetkova I, Serkedjieva Y, Bankova V, Christov R, Popov S. Antibacterial, antifungal and antiviral activity of propolis of different geographic origin. J Ethnopharmacol. 1999; 64(3): 235-40.
  26. Sforcin JM. Biological Properties and Therapeutic Applications of Propolis. Phytother Res. 2016; 30(6): 894-905.
  27. Vynograd N, Vynograd I, Sosnowski Z. A comparative multi-centre study of the efficacy of propolis, acyclovir and placebo in the treatment of genital herpes (HSV). Phytomedicine. 2000; 7(1): 1-6.
  28. Bueno-Silva B, Marsola A, Ikegaki M, Alencar SM, Rosalen PL. The effect of seasons on Brazilian red propolis and its botanical source: chemical composition and antibacterial activity. Nat Prod Res. 2017; 31(11): 1318-24.
  29. Xuan H, Wang Y, Li A, Fu C, Wang Y, Peng W. Bioactive Components of Chinese Propolis Water Extract on Antitumor Activity and Quality Control. Evid Based Complement Alternat Med. 2016; 2016: 9641965.
  30. Patel S. Emerging Adjuvant Therapy for Cancer: Propolis and its Constituents. J Diet Suppl. 2016; 13(3): 245-68.
  31. Alm-Eldeen AA, Basyony MA, Elfiky NK, Ghalwash MM. Effect of the Egyptian propolis on the hepatic antioxidant defense and pro-apoptotic p53 and anti-apoptotic bcl2 expressions in aflatoxin B1 treated male mice. Biomed Pharmacother. 2017; 87: 247-55.
  32. Russo A, Longo R, Vanella A. Antioxidant activity of propolis: role of caffeic acid phenethyl ester and galangin. Fitoterapia. 2002; 73 Suppl 1: S21-9.
  33. Sforcin JM. Propolis and the immune system: a review. J Ethnopharmacol. 2007; 113(1): 1-14.
  34. Bankova V. Chemical diversity of propolis and the problem of standardization. J Ethnopharmacol. 2005; 100(1-2): 114-7.
  35. Bufalo MC, Candeias JM, Sousa JP, Bastos JK, Sforcin JM. In vitro cytotoxic activity of Baccharis dracunculifolia and propolis against HEp-2 cells. Nat Prod Res. 2010; 24(18): 1710-8.
  36. Orsolic N, Sver L, Terzic S, Basic I. Peroral application of water-soluble derivative of propolis (WSDP) and its related polyphenolic compounds and their influence on immunological and antitumour activity. Vet Res Commun. 2005; 29(7): 575-93.
  37. Orsolic N, Saranovic AB, Basic I. Direct and indirect mechanism(s) of antitumour activity of propolis and its polyphenolic compounds. Planta Med. 2006; 72(1): 20-7.
  38. Kabala-Dzik A, Rzepecka-Stojko A, Kubina R, Jastrzebska-Stojko Z, Stojko R, Wojtyczka RD et al. Comparison of Two Components of Propolis: Caffeic Acid (CA) and Caffeic Acid Phenethyl Ester (CAPE) Induce Apoptosis and Cell Cycle Arrest of Breast Cancer Cells MDA-MB-231. Molecules. 2017; 22(9).
  39. Russo A, Acquaviva R, Campisi A, Sorrenti V, Di Giacomo C, Virgata G et al. Bioflavonoids as antiradicals, antioxidants and DNA cleavage protectors. Cell Biol Toxicol. 2000; 16(2): 91-8.
  40. van Acker SA, van den Berg DJ, Tromp MN, Griffioen DH, van Bennekom WP, van der Vijgh WJ et al. Structural aspects of antioxidant activity of flavonoids. Free Radic Biol Med. 1996; 20(3): 331-42.
  41. Iriti MV, Elena M. Brief Introduction to Polyphenols, Bioactive Phytochemicals for Human Health. Recent Advances in Medicinal Chemistry. Vol 2: Bentham Science; 2015: 3-9.
  42. You KM, Jong HG, Kim HP. Inhibition of cyclooxygenase/lipoxygenase from human platelets by polyhydroxylated/methoxylated flavonoids isolated from medicinal plants. Arch Pharm Res. 1999; 22(1): 18-24.
  43. Rzepecka-Stojko A, Stojko J, Kurek-Gorecka A, Gorecki M, Kabala-Dzik A, Kubina R et al. Polyphenols from Bee Pollen: Structure, Absorption, Metabolism and Biological Activity. Molecules. 2015; 20(12): 21732-49.
  44. Rzepecka-Stojko A, Kabala-Dzik A, Mozdzierz A, Kubina R, Wojtyczka RD, Stojko R et al. Caffeic Acid phenethyl ester and ethanol extract of propolis induce the complementary cytotoxic effect on triple-negative breast cancer cell lines. Molecules. 2015; 20(5): 9242-62.
  45. Kubina R, Kabala-Dzik A, Dziedzic A, Bielec B, Wojtyczka RD, Buldak RJ et al. The Ethanol Extract of Polish Propolis Exhibits Anti-Proliferative and/or Pro-Apoptotic Effect on HCT 116 Colon Cancer and Me45 Malignant Melanoma Cells In Vitro Conditions. Adv Clin Exp Med. 2015; 24(2): 203-12.
  46. Usman Amin M, Khurram M, Khan TA, Faidah HS, Ullah Shah Z, Ur Rahman S et al. Effects of Luteolin and Quercetin in Combination with Some Conventional Antibiotics against Methicillin-Resistant Staphylococcus aureus. Int J Mol Sci. 2016; 17(11).
  47. Iriti M, Varoni EM. Chemopreventive potential of flavonoids in oral squamous cell carcinoma in human studies. Nutrients. 2013; 5(7): 2564-76.
  48. Bortolotto LF, Barbosa FR, Silva G, Bitencourt TA, Beleboni RO, Baek SJ et al. Cytotoxicity of trans-chalcone and licochalcone A against breast cancer cells is due to apoptosis induction and cell cycle arrest. Biomed Pharmacother. 2017; 85: 425-33.
  49. Li RR, Pang LL, Du Q, Shi Y, Dai WJ, Yin KS. Apigenin inhibits allergen-induced airway inflammation and switches immune response in a murine model of asthma. Immunopharmacol Immunotoxicol. 2010; 32(3): 364-70.
  50. Shukla S, Bhaskaran N, Babcook MA, Fu P, Maclennan GT, Gupta S. Apigenin inhibits prostate cancer progression in TRAMP mice via targeting PI3K/Akt/FoxO pathway. Carcinogenesis. 2014; 35(2): 452-60.
  51. Silvan S, Manoharan S, Baskaran N, Anusuya C, Karthikeyan S, Prabhakar MM. Chemopreventive potential of apigenin in 7,12-dimethylbenz(a)anthracene induced experimental oral carcinogenesis. Eur J Pharmacol. 2011; 670(2-3): 571-7.
  52. Lee JH, Zhou HY, Cho SY, Kim YS, Lee YS, Jeong CS. Anti-inflammatory mechanisms of apigenin: inhibition of cyclooxygenase-2 expression, adhesion of monocytes to human umbilical vein endothelial cells, and expression of cellular adhesion molecules. Arch Pharm Res. 2007; 30(10): 1318-27.
  53. Silvan S, Manoharan S. Apigenin prevents deregulation in the expression pattern of cell-proliferative, apoptotic, inflammatory and angiogenic markers during 7,12-dimethylbenz[a]anthracene-induced hamster buccal pouch carcinogenesis. Arch Oral Biol. 2013; 58(1): 94-101.
  54. Su Q, Peng M, Zhang Y, Xu W, Darko KO, Tao T et al. Quercetin induces bladder cancer cells apoptosis by activation of AMPK signaling pathway. Am J Cancer Res. 2016; 6(2): 498-508.
  55. Tsai PH, Cheng CH, Lin CY, Huang YT, Lee LT, Kandaswami CC et al. Dietary Flavonoids Luteolin and Quercetin Suppressed Cancer Stem Cell Properties and Metastatic Potential of Isolated Prostate Cancer Cells. Anticancer Res. 2016; 36(12): 6367-80.
  56. Kanimozhi S, Subramanian P, Shanmugapriya S, Sathishkumar S. Role of Bioflavonoid Quercetin on Expression of Urea Cycle Enzymes, Astrocytic and Inflammatory Markers in Hyperammonemic Rats. Indian J Clin Biochem. 2017; 32(1): 68-73.
  57. Bors W, Heller W, Michel C, Saran M. Flavonoids as antioxidants: determination of radical-scavenging efficiencies. Methods Enzymol. 1990; 186: 343-55.
  58. Banjerdpongchai R, Wudtiwai B, Khawon P. Induction of Human Hepatocellular Carcinoma HepG2 Cell Apoptosis by Naringin. Asian Pac J Cancer Prev. 2016; 17(7): 3289-94.
  59. Kamaraj S, Ramakrishnan G, Anandakumar P, Jagan S, Devaki T. Antioxidant and anticancer efficacy of hesperidin in benzo(a)pyrene induced lung carcinogenesis in mice. Invest New Drugs. 2009; 27(3): 214-22.
  60. Parhiz H, Roohbakhsh A, Soltani F, Rezaee R, Iranshahi M. Antioxidant and anti-inflammatory properties of the citrus flavonoids hesperidin and hesperetin: an updated review of their molecular mechanisms and experimental models. Phytother Res. 2015; 29(3): 323-31.
  61. Siddiqi A, Hasan SK, Nafees S, Rashid S, Saidullah B, Sultana S. Chemopreventive efficacy of hesperidin against chemically induced nephrotoxicity and renal carcinogenesis via amelioration of oxidative stress and modulation of multiple molecular pathways. Exp Mol Pathol. 2015; 99(3): 641-53.
  62. Ahmadi A, Shadboorestan A, Nabavi SF, Setzer WN, Nabavi SM. The Role of Hesperidin in Cell Signal Transduction Pathway for the Prevention or Treatment of Cancer. Curr Med Chem. 2015; 22(30): 3462-71.
  63. Zhao Q, Zhao M, Parris AB, Xing Y, Yang X. Genistein targets the cancerous inhibitor of PP2A to induce growth inhibition and apoptosis in breast cancer cells. Int J Oncol. 2016; 49(3): 1203-10.
  64. Umeno A, Horie M, Murotomi K, Nakajima Y, Yoshida Y. Antioxidative and Antidiabetic Effects of Natural Polyphenols and Isoflavones. Molecules. 2016; 21(6).
  65. You F, Li Q, Jin G, Zheng Y, Chen J, Yang H. Genistein protects against Abeta25-35 induced apoptosis of PC12 cells through JNK signaling and modulation of Bcl-2 family messengers. BMC Neurosci. 2017; 18(1): 12.
  66. National Center for Biotechnology Information. PubChem Compound Database. CID=5280961. Available at: https://pubchem.ncbi.nlm.nih.gov/compound/5280961 Accessed 6 September, 2017.
  67. National Center for Biotechnology Information. PubChem Compound Database. CID=5280443. Available at: https://pubchem.ncbi.nlm.nih.gov/compound/5280443 Accessed 6 September, 2017.
  68. National Center for Biotechnology Information. PubChem Compound Database. CID=10621. Available at: https://pubchem.ncbi.nlm.nih.gov/compound/10621. Accessed 6 September, 2017.
  69. National Center for Biotechnology Information. PubChem Compound Database.CID=442428. Available at: https://pubchem.ncbi.nlm.nih.gov/compound/442428 Accessed 6 September, 2017.
  70. National Center for Biotechnology Information. PubChem Compound Database. CID=5280343. Available at: https://pubchem.ncbi.nlm.nih.gov/compound/5280343. Accessed 6 September, 2017.
  71. Kabala-Dzik A, Rzepecka-Stojko A, Kubina R, Jastrzebska-Stojko Z, Stojko R, Wojtyczka RD et al. Migration Rate Inhibition of Breast Cancer Cells Treated by Caffeic Acid and Caffeic Acid Phenethyl Ester: An In Vitro Comparison Study. Nutrients. 2017; 9(10).
  72. Borenfreund E, Puerner JA. Toxicity determined in vitro by morphological alterations and neutral red absorption. Toxicol Lett. 1985; 24(2-3): 119-24.
  73. Chahar MK, Sharma N, Dobhal MP, Joshi YC. Flavonoids: A versatile source of anticancer drugs. Pharmacogn Rev. 2011; 5(9): 1-12.
  74. Sak K. Cytotoxicity of dietary flavonoids on different human cancer types. Pharmacogn Rev. 2014; 8(16): 122-46.
  75. Bai H, Jin H, Yang F, Zhu H, Cai J. Apigenin induced MCF-7 cell apoptosis-associated reactive oxygen species. Scanning. 2014; 36(6): 622-31.
  76. Peng L, Wang B, Ren P. Reduction of MTT by flavonoids in the absence of cells. Colloids Surf B Biointerfaces. 2005; 45(2): 108-11.
  77. Uifalean A, Schneider S, Gierok P, Ionescu C, Iuga CA, Lalk M. The Impact of Soy Isoflavones on MCF-7 and MDA-MB-231 Breast Cancer Cells Using a Global Metabolomic Approach. Int J Mol Sci. 2016; 17(9).
  78. Febriansah R, Putri DD, Sarmoko, Nurulita NA, Meiyanto E, Nugroho AE. Hesperidin as a preventive resistance agent in MCF-7 breast cancer cells line resistance to doxorubicin. Asian Pac J Trop Biomed. 2014; 4(3): 228-33.
  79. Ranganathan S, Halagowder D, Sivasithambaram ND. Quercetin Suppresses Twist to Induce Apoptosis in MCF-7 Breast Cancer Cells. PLoS One. 2015; 10(10): e0141370.
  80. Lu YH, Su MY, Huang HY, Lin L, Yuan CG. Protective effects of the citrus flavanones to PC12 cells against cytotoxicity induced by hydrogen peroxide. Neurosci Lett. 2010; 484(1): 6-11.
  81. Tsuboy MS, Marcarini JC, de Souza AO, de Paula NA, Dorta DJ, Mantovani MS et al. Genistein at maximal physiologic serum levels induces G0/G1 arrest in MCF-7 and HB4a cells, but not apoptosis. J Med Food. 2014; 17(2): 218-25.
  82. Saiprasad G, Chitra P, Manikandan R, Sudhandiran G. Hesperidin induces apoptosis and triggers autophagic markers through inhibition of Aurora-A mediated phosphoinositide-3-kinase/Akt/mammalian target of rapamycin and glycogen synthase kinase-3 beta signalling cascades in experimental colon carcinogenesis. Eur J Cancer. 2014; 50(14): 2489-507.
  83. Banjerdpongchai R, Wudtiwai B, Khaw-On P, Rachakhom W, Duangnil N, Kongtawelert P. Hesperidin from Citrus seed induces human hepatocellular carcinoma HepG2 cell apoptosis via both mitochondrial and death receptor pathways. Tumour Biol. 2016; 37(1): 227-37.
  84. Li H, Yang B, Huang J, Xiang T, Yin X, Wan J et al. Naringin inhibits growth potential of human triple-negative breast cancer cells by targeting beta-catenin signaling pathway. Toxicol Lett. 2013; 220(3): 219-28.
  85. Choi EJ, Bae SM, Ahn WS. Antiproliferative effects of quercetin through cell cycle arrest and apoptosis in human breast cancer MDA-MB-453 cells. Arch Pharm Res. 2008; 31(10): 1281-5.
  86. Rivera Rivera A, Castillo-Pichardo L, Gerena Y, Dharmawardhane S. Anti-Breast Cancer Potential of Quercetin via the Akt/AMPK/Mammalian Target of Rapamycin (mTOR) Signaling Cascade. PLoS One. 2016; 11(6): e0157251.
  87. Tseng TH, Chien MH, Lin WL, Wen YC, Chow JM, Chen CK et al. Inhibition of MDA-MB-231 breast cancer cell proliferation and tumor growth by apigenin through induction of G2/M arrest and histone H3 acetylation-mediated p21WAF1/CIP1 expression. Environ Toxicol. 2017; 32(2): 434-44.
  88. Lin CH, Chang CY, Lee KR, Lin HJ, Chen TH, Wan L. Flavones inhibit breast cancer proliferation through the Akt/FOXO3a signaling pathway. BMC Cancer. 2015; 15: 958.
  89. Dourado GK, Stanilka JM, Percival SS, Cesar TB. Chemopreventive Actions of Blond and Red-Fleshed Sweet Orange Juice on the Loucy Leukemia Cell Line. Asian Pac J Cancer Prev. 2015; 16(15): 6491-9.
  90. Kim DI, Lee SJ, Lee SB, Park K, Kim WJ, Moon SK. Requirement for Ras/Raf/ERK pathway in naringin-induced G1-cell-cycle arrest via p21WAF1 expression. Carcinogenesis. 2008; 29(9): 1701-9.
  91. Yang L, Liu Y, Wang M, Qian Y, Dong X, Gu H et al. Quercetin-induced apoptosis of HT-29 colon cancer cells via inhibition of the Akt-CSN6-Myc signaling axis. Mol Med Rep. 2016; 14(5): 4559-66.
  92. Nabavi SM, Habtemariam S, Daglia M, Nabavi SF. Apigenin and Breast Cancers: From Chemistry to Medicine. Anticancer Agents Med Chem. 2015; 15(6): 728-35.
  93. Long X, Fan M, Bigsby RM, Nephew KP. Apigenin inhibits antiestrogen-resistant breast cancer cell growth through estrogen receptor-alpha-dependent and estrogen receptor-alpha-independent mechanisms. Mol Cancer Ther. 2008; 7(7): 2096-108.
  94. Mak P, Leung YK, Tang WY, Harwood C, Ho SM. Apigenin suppresses cancer cell growth through ERbeta. Neoplasia. 2006; 8(11): 896-904.
  95. Fang Y, Zhang Q, Wang X, Yang X, Wang X, Huang Z et al. Quantitative phosphoproteomics reveals genistein as a modulator of cell cycle and DNA damage response pathways in triple-negative breast cancer cells. Int J Oncol. 2016; 48(3): 1016-28.
  96. Zhang L, Yang B, Zhou K, Li H, Li D, Gao H et al. Potential therapeutic mechanism of genistein in breast cancer involves inhibition of cell cycle regulation. Mol Med Rep. 2015; 11(3): 1820-6.
  97. Kaur M, Badhan RK. Phytochemical mediated-modulation of the expression and transporter function of breast cancer resistance protein at the blood-brain barrier: An in-vitro study. Brain Res. 2017; 1654(Pt A): 9-23.
  98. Schindler R, Mentlein R. Flavonoids and vitamin E reduce the release of the angiogenic peptide vascular endothelial growth factor from human tumor cells. J Nutr. 2006; 136(6): 1477-82.
  99. Nguyen LT, Lee YH, Sharma AR, Park JB, Jagga S, Sharma G et al. Quercetin induces apoptosis and cell cycle arrest in triple-negative breast cancer cells through modulation of Foxo3a activity. Korean J Physiol Pharmacol. 2017; 21(2): 205-13.
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