Oleuropein Induces Apoptosis Via the p53 Pathway in Breast Cancer Cells

  • Hassan, Zeinab Korany (Department of Zoology, College of Science, King Saud University) ;
  • Elamin, Maha Hussein (Department of Zoology, College of Science, King Saud University) ;
  • Omer, Sawsan Ali (Department of Zoology, College of Science, King Saud University) ;
  • Daghestani, Maha Hassan (Department of Zoology, College of Science, King Saud University) ;
  • Al-Olayan, Ebtesam Salah (Department of Zoology, College of Science, King Saud University) ;
  • Elobeid, Mai AbdelRahman (Department of Zoology, College of Science, King Saud University) ;
  • Virk, Promy (Department of Zoology, College of Science, King Saud University)
  • Published : 2013.11.30


Background: Breast cancer is a major health problem worldwide. Olive oil induces apoptosis in some cancer cells due to phenolic compounds like oleuropein. Although oleuropein has anticancer activity, the underlying mechanisms of action remain unknown. The study aimed to assess the mechanism of oleuropin-induced breast cancer cell apoptosis. Materials and Methods: p53, Bcl-2 and Bax gene expression was evaluated by semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) in luminal MCF-7 cells. Results: Oleuropein-induced apoptosis was accompanied by up-regulation of both p53 and Bax gene expression levels and down-regulation in Bcl2. Conclusions: Oleuropein induces apoptosis in breast tumour cells via a p53-dependent pathway mediated by Bax and Bcl2 genes. Therefore, oleuropein may have therapeutic potential in breast cancer patients by inducing apoptosis via activation of the p53 pathway.


Apoptotic pathway;Bax gene;breast cancer;Bcl2 gene;oleuropein;p53 gene;semi-quantitative RT-PCR


  1. Abe R, Beckett J, Nixon A, et al (2011). Olive oil polyphenol oleuropein inhibits smooth muscle cell proliferation. Eur J Vasc Endovasc Surg, 41, 814-20.
  2. Borresen-Dale AL (2003). TP53 and breast cancer. Hum Mutat, 21, 292-300.
  3. Campolo M, Di Paola R, Impellizzeri D, et al (2013). Effects of a polyphenol present in olive oil, oleuropein aglycone, in a murine model of intestinal ischemia/reperfusion injury. J Leukoc Biol, 93, 277-87.
  4. Chipuk JE, Kuwana T, Bouchier-Hayes L, et al (2004). Direct activation of Bax by p53 mediates mitochondrial membrane permeabilization and apoptosis. Science, 303, 1010-4.
  5. Choudhuri T, Pal S, Agwarwal ML, Das T, Sa G (2002). Curcumin induces apoptosis in human breast cancer cells through p53-dependent Bax induction. FEBS Lett, 512, 334-40.
  6. Das T, Sa G, Sinha P, Ray PK (1999). Induction of cell proliferation and apoptosis: dependence on the dose of the inducer. Biochem Biophys Res Commun, 260, 105-10.
  7. Elamin MH, Daghestani MH, Omer SA, et al (2013). Olive oil oleuropein has anti-breast cancer properties with higher efficiency on ER-negative cells. Food Chem Toxicol, 53, 310-6.
  8. Fridman JS, Lowe SW (2003). Control of apoptosis by p53. Oncogene, 22, 9030-40.
  9. Hassan ZK, Elamin MH, Daghestani MH, et al (2012). Oleuropein induces anti-metastatic effects in breast cancer. Asian Pac J Cancer Prev, 13, 4555-9.
  10. Hollstein M, Sidransky D, Vogelstein B, Harris CC (1991). p53 mutations in human cancers. Science, 253, 49-53.
  11. Huang KF, Zhang GD, Huang YQ, Diao Y (2012). Wogonin induces apoptosis and down-regulates survivin in human breast cancer MCF-7 cells by modulating PI3K-AKT pathway. Int Immunopharmacol, 12, 334-41.
  12. Jemal A, Bray F, Center MM, et al (2011). Global cancer statistics. CA Cancer J Clin, 61, 69-90.
  13. Kirkin V, Joos S, Zornig M (2004). The role of Bcl-2 family members in tumorigenesis. Biochim Biophys Acta, 1644, 229-49.
  14. Kostomoiri M, Fragkouli A, Sagnou M, et al (2013). Oleuropein, an anti-oxidant polyphenol constituent of olive promotes alpha-secretase cleavage of the amyloid precursor protein (AbetaPP). Cell Mol Neurobiol, 33, 147-54.
  15. Lessene G, Czabotar PE, Colman PM (2008). BCL-2 family antagonists for cancer therapy. Nat Rev Drug Discov, 7, 989-1000.
  16. Li-Weber M (2009). New therapeutic aspects of flavones: the anticancer properties of Scutellaria and its main active constituents Wogonin, Baicalein and Baicalin. Cancer Treat Rev, 35, 57-68.
  17. Moon DO, Lee KJ, Choi YH, Kim GY (2007). Beta-sitosterol-induced-apoptosis is mediated by the activation of ERK and the downregulation of Akt in MCA-102 murine fibrosarcoma cells. Int Immunopharmacol, 7, 1044-53.
  18. Oi-Kano Y, Kawada T, Watanabe T, et al (2013). Oleuropein supplementation increases urinary noradrenaline and testicular testosterone levels and decreases plasma corticosterone level in rats fed high-protein diet. J Nutr Biochem, 24, 887-93.
  19. Parzonko A, Czerwinska ME, Kiss AK, Naruszewicz M (2013). Oleuropein and oleacein may restore biological functions of endothelial progenitor cells impaired by angiotensin II via activation of Nrf2/heme oxygenase-1 pathway. Phytomedicine, 20, 1088-94.
  20. Pasban-Aliabadi H, Esmaeili-Mahani S, Sheibani V, et al (2013). Inhibition of 6-hydroxydopamine-induced PC12 cell apoptosis by olive (Olea europaea L.) leaf extract is performed by its main component oleuropein. Rejuvenation Res, 16, 134-42.
  21. Saad ED (2011). Endpoints in advanced breast cancer: methodological aspects and clinical implications. Indian J Med Res, 134, 413-8.
  22. Santiago-Mora R, Casado-Diaz A, De Castro MD, Quesada-Gomez JM (2011). Oleuropein enhances osteoblastogenesis and inhibits adipogenesis: the effect on differentiation in stem cells derived from bone marrow. Osteoporos Int, 22, 675-84.
  23. Sirianni R, Chimento A, De Luca A, et al (2010). Oleuropein and hydroxytyrosol inhibit MCF-7 breast cancer cell proliferation interfering with ERK1/2 activation. Mol Nutr Food Res, 54, 833-40.
  24. Struckhoff AP, Patel B, Beckman BS (2010). Inhibition of p53 sensitizes MCF-7 cells to ceramide treatment. Int J Oncol 37, 21-30.
  25. Taylor WR, Agarwal ML, Agarwal A, Stacey DW, Stark GR (1999). p53 inhibits entry into mitosis when DNA synthesis is blocked. Oncogene, 18, 283-95.
  26. Zare L, Esmaeili-Mahani S, Abbasnejad M, et al (2012). Oleuropein, chief constituent of olive leaf extract, prevents the development of morphine antinociceptive tolerance through inhibition of morphine-induced L-type calcium channel overexpression. Phytother Res, 26, 1731-7.

Cited by

  1. Emodin-Provoked Oxidative Stress Induces Apoptosis in Human Colon Cancer HCT116 Cells through a p53-Mitochondrial Apoptotic Pathway vol.15, pp.13, 2014,
  2. Ubiquitination of p53 is Involved in Troglitazone Induced Apoptosis in Cervical Cancer Cells vol.15, pp.5, 2014,
  3. Rice Bran Phytic Acid Induced Apoptosis Through Regulation of Bcl-2/Bax and p53 Genes in HepG2 Human Hepatocellular Carcinoma Cells vol.15, pp.8, 2014,
  4. Rapamycin and PF4 Induce Apoptosis by Upregulating Bax and Down-Regulating Survivin in MNU-Induced Breast Cancer vol.15, pp.9, 2014,
  5. Oleuropein induces apoptosis via activation of caspases and suppression of phosphatidylinositol 3-kinase/protein kinase B pathway in HepG2 human hepatoma cell line vol.11, pp.6, 2015,
  6. Phytochemical Properties and Anti-Proliferative Activity of Olea europaea L. Leaf Extracts against Pancreatic Cancer Cells vol.20, pp.7, 2015,
  7. Protease activated receptor-2 (PAR2): possible target of phytochemicals vol.33, pp.9, 2015,
  8. Evidence to Support the Anti-Cancer Effect of Olive Leaf Extract and Future Directions vol.8, pp.8, 2016,
  9. Oleuropein and Cancer Chemoprevention: The Link is Hot vol.22, pp.5, 2017,
  10. Anticancer effects of oleuropein vol.43, pp.4, 2017,
  11. Polyphenols as Promising Drugs against Main Breast Cancer Signatures vol.6, pp.4, 2017,
  12. Oleuropein represses the radiation resistance of ovarian cancer by inhibiting hypoxia and microRNA-299-targetted heparanase expression vol.8, pp.8, 2017,
  13. Synergistic Interplay between Curcumin and Polyphenol-Rich Foods in the Mediterranean Diet: Therapeutic Prospects for Neurofibromatosis 1 Patients vol.9, pp.7, 2017,
  14. Mediterranean Diet and Invasive Breast Cancer Risk Among Women at High Cardiovascular Risk in the PREDIMED Trial vol.175, pp.11, 2015,
  15. Nutraceutical Properties of Olive Oil Polyphenols. An Itinerary from Cultured Cells through Animal Models to Humans vol.17, pp.6, 2016,
  16. Potential Health Benefits of Olive Oil and Plant Polyphenols vol.19, pp.3, 2018,
  17. Simultaneous downregulation of miR-21 and miR-155 through oleuropein for breast cancer prevention and therapy vol.119, pp.9, 2018,
  18. Oleuropein inhibits migration ability through suppression of epithelial-mesenchymal transition and synergistically enhances doxorubicin-mediated apoptosis in MCF-7 cells pp.00219541, 2018,
  19. Phenolic Compounds Isolated from Olive Oil as Nutraceutical Tools for the Prevention and Management of Cancer and Cardiovascular Diseases vol.19, pp.8, 2018,
  20. The Olive Biophenols Oleuropein and Hydroxytyrosol Selectively Reduce Proliferation, Influence the Cell Cycle, and Induce Apoptosis in Pancreatic Cancer Cells vol.19, pp.7, 2018,
  21. Olive Oil Nutraceuticals in the Prevention and Management of Diabetes: From Molecules to Lifestyle vol.19, pp.7, 2018,
  22. Antitumor Perspectives of Oleuropein and Its Metabolite Hydroxytyrosol: Recent Updates vol.83, pp.7, 2018,
  23. via oleuropein as a potent prevention and therapeutic agent in MCF-7 breast cancer cells pp.07302312, 2019,
  24. Oleuropein inhibits esophageal cancer through hypoxic suppression of BTG3 mRNA vol.10, pp.2, 2019,