Olive leaf extract containing oleuropein modulates the cytotoxic effect of epirubicin on breast cancer cells depending on the cell line

Seniz Korkmaz 1 , Mehmet Sarimahmut 2 , Mustafa Zafer Ozel 3  and Engin Ulukaya 4
  • 1 Uludag University, Medical School, Department of Medical Biochemistry, Bursa, Turkey
  • 2 Uludag University, Faculty of Arts and Science, Department of Biology, Bursa, Turkey
  • 3 University of York, School of Chemistry, Heslington, York YO10 5DD, United Kingdom of Great Britain and Northern Ireland
  • 4 Uludag University, Medical School, Department of Medical Biochemistry, Bursa, Turkey, Tel.: +90 224 295 3913, Fax: +90 224 442 8245
Seniz Korkmaz, Mehmet Sarimahmut, Mustafa Zafer Ozel and Engin Ulukaya

Abstract

Objective:

Epidemiologic studies showed that nutrition plays a role in incidence of cancer. However, little is known if nutrition also modulates the effect of chemotherapeutics. For this purpose, the present study investigates the cytotoxic effect of olive leaf extract and its combination with epirubicin.

Method:

Cell viability was measured via ATP assay on MDA-MB-231 and MCF-7 cell lines. Apoptosis was detected by poly(ADP-ribose) polymerase (PARP) cleavage, and the expression of apoptosis-related genes. A single extract was used throughout the study.

Results:

Both olive leaf extract and epirubicin resulted in cytotoxic effect in a dose-dependent manner in both cell lines. The extract further increased the cytotoxic effect of epirubicin in MDA-MB-231 cell line. However, in contrast, it abolished the cytotoxic effect of epirubicin in MCF-7 cell line. As a confirmative result, the increased expressions of FASLG and HRK following epirubicin treatment were down-regulated when epirubicin was used in combination with the extract in MCF-7 cells.

Conclusion:

Olive leaf extract modulates the cytotoxic effect of epirubicin when it is in combination depending on the type of cell line. This warrants further in vivo experiments for better understanding of this intriguing result.

    • Supplementary material
  • 1.

    Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, et al. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide. IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer, 2013.

  • 2.

    Lairon D. Intervention studies on Mediterranean diet and cardiovascular risk. Mol Nutr Food Res 2007;51:1209–14.

    • PubMed
    • Export Citation
  • 3.

    Pelucchi C, Bosetti C, Rossi M, Negri E, La Vecchia C. Selected aspects of Mediterranean diet and cancer risk. Nutr Cancer 2009;61:756–66.

    • Crossref
    • PubMed
    • Export Citation
  • 4.

    Samet I, Han J, Jlaiel L, Sayadi S, Isoda H. Olive (Olea europaea) leaf extract induces apoptosis and monocyte/macrophage differentiation in human chronic myelogenous leukemia K562 cells: insight into the underlying mechanism. Oxid Med Cell Longev 2014;2014:1–16.

  • 5.

    Bouallagui Z, Han J, Isoda H, Sayadi S. Hydroxytyrosol rich extract from olive leaves modulates cell cycle progression in MCF-7 human breast cancer cells. Food Chem Toxicol 2011;49:179–184.

    • Crossref
    • PubMed
    • Export Citation
  • 6.

    Fares R, Bazzi S, Baydoun SE, Abdel-Massih, RM. The antioxidant and anti-proliferative activity of the Lebanese Olea europaea extract. Plant Food Hum Nutr 2011;66:58–63.

    • Crossref
    • Export Citation
  • 7.

    Goulas V, Exarchou V, Troganis AN, Psomiadou E, Fotsis T, Briasoulis E, et al. Phytochemicals in olive-leaf extracts and their antiproliferative activity against cancer and endothelial cells. Mol Nutr Food Res 2009;53:600–08.

    • Crossref
    • PubMed
    • Export Citation
  • 8.

    Mijatovic SA, Timotijevic GS, Miljkovic DM, Radovic JM, Maksimovic‐Ivanic DD, Dekanski DP, et al. Multiple antimelanoma potential of dry olive leaf extract. Int J Cancer 2011;128:1955–65.

    • Crossref
    • PubMed
    • Export Citation
  • 9.

    Minotti G, Menna P, Salvatorelli E, Cairo G, Gianni L. Anthracyclines: molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacol Rev 2004;56:185–229.

    • Crossref
    • PubMed
    • Export Citation
  • 10.

    Esteva FJ, Valero V, Pusztai L, Boehnke-Michaud L, Buzdar AU, Hortobagyi GN. Chemotherapy of metastatic breast cancer: what to expect in 2001 and beyond. Oncologist 2001;6:133–46.

    • Crossref
    • PubMed
    • Export Citation
  • 11.

    Mitri Z, Karakas C, Wei C, Birones B, Simmons H, Ibrahim N, et al. A phase 1 study with dose expansion of the CDK inhibitor dinaciclib (SCH 727965) in combination with epirubicin in patients with metastatic triple negative breast cancer. Invest New Drugs 2015;33:890–4.

    • Crossref
    • PubMed
    • Export Citation
  • 12.

    Roche H, De Benedictis, Cottura E, Govi S, Dalenc F, Locatelli A, et al. A phase I study of ixabepilone in combination with epirubicin in patients with metastatic breast cancer. Clin Breast Cancer 2012;12:167–74.

    • Crossref
    • PubMed
    • Export Citation
  • 13.

    Andreotti PE, Cree IA, Kurbacher CM, Hartmann DM, Linder D, Harel G, et al. Chemosensitivity testing of human tumors using a microplate adenosine triphosphate luminescence assay: clinical correlation for cisplatin resistance of ovarian carcinoma. Cancer Res 1995;55:5276–82.

    • PubMed
    • Export Citation
  • 14.

    Ari F, Ulukaya E, Sarimahmut M, Yilmaz VT. Palladium(II) saccharinate complexes with bis(2-pyridylmethyl) amine induce cell death by apoptosis in human breast cancer cells in vitro. Bioorgan Med Chem 2013;21:3016–21.

    • Crossref
    • Export Citation
  • 15.

    Abaza L, Talorete TP, Yamada P, Kurita Y, Zarrouk M, Isoda H. Induction of growth inhibition and differentiation of human leukemia HL-60 cells by a Tunisian gerboui olive leaf extract. Biosci Biotech Bioch 2007;71:1306–12.

    • Crossref
    • Export Citation
  • 16.

    Sudjana AN, D’Orazio C, Ryan V, Rasool N, Ng J, Islam N, et al. Antimicrobial activity of commercial Olea europaea (olive) leaf extract. Int J Antimicrob Agents 2009;33:461–3.

    • Crossref
    • PubMed
    • Export Citation
  • 17.

    Visioli F, Galli C. Biological properties of olive oil phytochemicals. Crit Rev Food Sci Nutr 2002;42:209–21.

    • Crossref
    • PubMed
    • Export Citation
  • 18.

    Visioli F, Bellosta S, Galli C. Oleuropein, the bitter principle of olives, enhances nitric oxide production by mouse macrophages. Life Sci 1998;62:541–6.

    • Crossref
    • PubMed
    • Export Citation
  • 19.

    Han J, Talorete TP, Yamada P, Isoda H. Anti-proliferative and apoptotic effects of oleuropein and hydroxytyrosol on human breast cancer MCF-7 cells. Cytotechnology 2009;59:45–53.

    • Crossref
    • PubMed
    • Export Citation
  • 20.

    Menendez JA, Vazquez-Martin A, Colomer R, Brunet J, Carrasco-Pancorbo A, Garcia-Villalba R, et al. Olive oil’s bitter principle reverses acquired autoresistance to trastuzumab (Herceptin™) in HER2-overexpressing breast cancer cells. BMC Cancer 2007;7:80–98.

    • Crossref
    • Export Citation
  • 21.

    Aggarwal BB, Shishodia S. Molecular targets of dietary agents for prevention and therapy of cancer. Biochem Pharmacol 2006;71:1397–421.

    • Crossref
    • PubMed
    • Export Citation
  • 22.

    Fini L, Hotchkiss E, Fogliano V, Graziani G, Romano M, De Vol EB, et al. Chemopreventive properties of pinoresinol-rich olive oil involve a selective activation of the ATM-p53 cascade in colon cancer cell lines. Carcinogenesis 2008;29:139–46.

    • Crossref
    • PubMed
    • Export Citation
  • 23.

    Obied HK, Prenzler PD, Konczak I, Rheman A, Robard K. Chemistry and bioactivity of olive biophenols in some antioxidant and antiproliferative in vitro bioassays. Chem Res Toxicol 2009;22:227–34.

    • Crossref
    • PubMed
    • Export Citation
  • 24.

    Hamdi KH, Castellon R. Oleuropein, a non-toxic olive iridoid, is an anti-tumor agent and cytoskeleton disruptor. Biochem Biophys Res Commun 2005;334:769–78.

    • Crossref
    • PubMed
    • Export Citation
  • 25.

    Fu S, Arraez-Roman D, Segura-Carretero A, Menendez JA, Menendez-Gutierrez MP, Micol V, et al. Qualitative screening of phenolic compounds in olive leaf extracts by hyphenated liquid chromatography and preliminary evaluation of cytotoxic activity against human breast cancer cells. Anal Bioanal Chem 2010;397:643–54.

    • Crossref
    • PubMed
    • Export Citation
  • 26.

    Anter J, Fernandez-Bedmar Z, Villatoro-Pulido M, Demyda-Peyras S, Moreno-Millan M, Alonso-Moraga A, et al. A pilot study on the DNA- protective, cytotoxic, and apoptosis-inducing properties of olive-leaf extracts. Mutat Res 2011;723:165–70.

    • Crossref
    • PubMed
    • Export Citation
  • 27.

    Sun WL, Chen J, Wang YP, Zheng H. Autophagy protects breast cancer cells from epirubicin-induced apoptosis and facilitates epirubicin-resistance development. Autophagy 2011;7: 1035–44.

    • Crossref
    • PubMed
    • Export Citation
  • 28.

    Yang Y, Zhao S, Song J. Caspase-dependent apoptosis and-independent poly (ADP-ribose) polymerase cleavage induced by transforming growth factor β1. Int J Biochem Cell B 2004;36:223–34.

    • Crossref
    • Export Citation
  • 29.

    Adlercreutz H, Bannwart C, Wahala K, Makela T, Brunow G, Hase T, et al. Inhibition of human aromatase by mammalian lignans and isoflavonoid phytoestrogens. J Steroid Biochem 1993;44:147–56.

    • Crossref
    • Export Citation
  • 30.

    Elamin MH, Daghestani MH, Omer SA, Elobeid MA, Virk P, Al-Olayan EM, et al. Olive oil oleuropein has anti-breast cancer properties with higher efficiency on ER-negative cells. Food Chem Toxicol 2013;53:310–6.

    • Crossref
    • PubMed
    • Export Citation
  • 31.

    Sirianni R, Chimento A, De Luca A, Casaburi I, Rizza P, Onofrio A, et al. Oleuropein and hydroxytyrosol inhibit MCF‐7 breast cancer cell proliferation interfering with ERK1/2 activation. Mol Nutr Food Res 2010;54:833–40.

    • Crossref
    • PubMed
    • Export Citation
Purchase article
Get instant unlimited access to the article.
$42.00
Log in
Already have access? Please log in.


or
Log in with your institution

Journal + Issues

Turkish Journal of Biochemistry (TJB), official journal of Turkish Biochemical Society, is issued electronically every 2 months. The main aim of the journal is to support the research and publishing culture by ensuring that every published manuscript has an added value and thus providing international acceptance of the “readability” of the manuscripts published in the journal.

Search