Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Turkish Journal of Biochemistry

Türk Biyokimya Dergisi


IMPACT FACTOR 2018: 0.329

CiteScore 2018: 0.28

SCImago Journal Rank (SJR) 2018: 0.138
Source Normalized Impact per Paper (SNIP) 2018: 0.169

Online
ISSN
1303-829X
See all formats and pricing
More options …
Volume 41, Issue 6

Issues

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

Oleuropein içeren zeytin yaprağı ekstresi hücre hattına bağlı olarak meme kanser hücrelerinde epirubisinin sitotoksik etkilerini değiştirir

Seniz Korkmaz / Mehmet Sarimahmut / Mustafa Zafer Ozel
  • University of York, School of Chemistry, Heslington, York YO10 5DD, United Kingdom of Great Britain and Northern Ireland
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Engin Ulukaya
  • Corresponding author
  • Uludag University, Medical School, Department of Medical Biochemistry, Bursa, Turkey, Tel.: +90 224 295 3913, Fax: +90 224 442 8245
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2016-09-26 | DOI: https://doi.org/10.1515/tjb-2016-0117

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.

Özet

Amaç:

Epidemiyolojik çalışmalar beslenmenin kanser insidansında önemli bir rolü olduğunu göstermektedir. Ancak, beslenmenin kemoterapinin de etkilerini değiştirip değiştirmediğiyle ilgili az şey bilinmektedir. Bu amaçla, bu çalışma zeytin yaprağı ekstresi ve epirubisin ile kombinasyonunun sitotoksik etkilerini araştırmaktadır.

Metod:

Hücre canlılığı ATP testi kullanılarak MDA-MB-231 ve MCF-7 hücre hatlarında ölçülmüştür. Apoptozis, poli-(ADP-riboz) polimeraz (PARP) kırılması ve apoptozis ilişkili genlerin ifadeleri kullanılarak saptanmıştır. Çalışma boyunca tek bir ekstre kullanılmıştır.

Bulgular:

Hem zeytin yaprağı ekstresi hem epirubisin doza bağlı olarak her iki hücre hattında da sitotoksik etkiye neden olmştur. Ekstre, MDA-MB-231 hücre hattında epirubisinin sitotoksik etkisini daha da arttırmıştır. Ancak buna karşın, MCF-7 hücre hattında epirubisinin sitotoksik etkisini bozmuştur. Doğrulayıcı bir sonuç olarak, MCF-7 hücrelerinde epirubisin uygulamasıyla artan FASLG ve HRK ifadeleri, epirubisin ekstre ile kombinasyon halinde kullanıldığında düşmüştür.

Sonuç:

Zeytin yaprağı ekstresi epirubisin ile kombinasyon halinde kullanıldığında epirubisinin sitotoksik etkilerini hücre hattına bağlı olarak değiştirir. Bu ilgi çekici sonuçların daha iyi anlaşılması için ileri in vivo deneylerin yapılmasını gerektirmektedir.

This article offers supplementary material which is provided at the end of the article.

Keywords: Olive leaf extract; Breast cancer cell lines; Apoptosis; Cytotoxicity; Epirubicin

Anahtar kelimeler:: Zeytin yaprağı ekstresi; Meme kanseri hücre hatları; Apoptosis; Sitotoksisite; Epirubisin

References

  • 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.Google Scholar

  • 2.

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

  • 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.Google Scholar

  • 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.Google Scholar

  • 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.Google Scholar

  • 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.Google Scholar

  • 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.Google Scholar

  • 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.Google Scholar

  • 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.Google Scholar

  • 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.Google Scholar

  • 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.Google Scholar

  • 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.Google Scholar

  • 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.Google Scholar

  • 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.Google Scholar

  • 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.Google Scholar

  • 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.Google Scholar

  • 17.

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

  • 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.Google Scholar

  • 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.Google Scholar

  • 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.Google Scholar

  • 21.

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

  • 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.Google Scholar

  • 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.Google Scholar

  • 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.Google Scholar

  • 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.Google Scholar

  • 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.Google Scholar

  • 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.Google Scholar

  • 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.Google Scholar

  • 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.Google Scholar

  • 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.Google Scholar

  • 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.Google Scholar

About the article

aSeniz Korkmaz and Mehmet Sarimahmut: These authors contributed equally to this work.


Received: 2015-09-15

Accepted: 2016-02-12

Published Online: 2016-09-26

Published in Print: 2016-12-01


Conflict of Interest Statement: The authors have no conflict of interest.


Citation Information: Turkish Journal of Biochemistry, Volume 41, Issue 6, Pages 385–392, ISSN (Online) 1303-829X, ISSN (Print) 0250-4685, DOI: https://doi.org/10.1515/tjb-2016-0117.

Export Citation

©2016 Walter de Gruyter GmbH, Berlin/Boston.Get Permission

Supplementary Article Materials

Comments (0)

Please log in or register to comment.
Log in