Skip to main content
SpringerLink
Log in

Oleuropein exhibits anticarcinogen effects against gastric cancer cell lines

  • Original Article
  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Background

Oleuropein (OLE), the main phenolic compound of the olive fruit and leaves, has many heathful effects. Gastric cancer is the most fatal malignancy in many parts of the world and it is generally related to harmful dietetic factors. The anticarcinogenic role of OLE in gastric cancer has not been studied sufficiently yet. In this study, we aimed to research the cytotoxic, genotoxic and apoptotic effects of OLE on gastric adenocancer (AGS) cells in vitro.

Methods and Results

A standard cell line derived from gastric adeno cancer (AGS) cells was employed, and its performance following a 24-hour exposure to OLE at various doses was examined. The ATP cell viability assay, 2’,7’-dichlorodihydrofluorescein-diacetate assay (H2DCF-DA) and alkaline single cell gel electrophoresis assay (Comet Assay) were used to study the cytotoxicity, production of reactive oxygen species (ROS) and genotoxicity respectively. The induction of apoptosis was discovered using flow cytometry. OLE reduced AGS cells viability about 60% at maximum concentration (500 µmol/L) and also resulted in approximately 100% DNA damage and about 40% apoptosis with necrosis in AGS cells depending on the increased doses. Cell viability was also significantly decreased in relation to increased intracellular reactive oxygen species (ROS) levels (p < 0.05 − 0.001).

Conclusions

Oleuropein has shown significant anticarcinogen effects against gastric adenocancer (AGS) cells in vitro. Oleuropein, a nutrient rich in olive and olive oil, seems to be both protective and therapeutic against gastric cancer and may be a new chemotherapeutic agent in the future.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5a
Fig. 5b

Similar content being viewed by others

Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

References

  1. Nediani C, Ruzzolini J, Romani A, Calorini L (2019) Oleuropein, a bioactive compound from Olea europaea L., as a potential preventive and therapeutic agent in non-communicable diseases. Antioxidants 8(12):578. https://doi.org/10.3390/antiox8120578

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Zheng Y, Liu Z, Yang X, Liu L, Ahn KS (2021) An updated review on the potential antineoplastic actions of oleuropein. Phytother Res 36(1):365–379. https://doi.org/10.1002/ptr.7325

    Article  CAS  PubMed  Google Scholar 

  3. Antoniou C, Hull J (2021) The anti-cancer effect of Olea europaea L. products: a review. Curr Nutr Rep 10:99–124. https://doi.org/10.1007/s13668-021-00350-8

    Article  PubMed  PubMed Central  Google Scholar 

  4. Fabiani R, Rosignoli P, De Bartolomeo A, Fuccelli R, Morozzi G (2008) Inhibition of cell cycle progression by hydroxytyrosol is associated with upregulation of cyclin-dependent protein kinase inhibitors p21(WAF1/Cip1) and p27(Kip1) and with induction of differentiation in HL60 cells. J Nutr 138(1):42–48. https://doi.org/10.1093/jn/138.1.42

    Article  CAS  PubMed  Google Scholar 

  5. Rizzo M, Ventrice D, Giannetto F, Cirinnà S, Santagati NA, Procopio A et al (2017) Antioxidant activity of oleuropein and semisynthetic acetylderivatives determined by measuring malondialdehyde in rat brain. J Pharm Pharmacol 69(11):1502–1512. https://doi.org/10.1111/jphp.12807

    Article  CAS  PubMed  Google Scholar 

  6. Geyikoglu F, Isikgoz H, Onalan H, Colak S, Cerig S, Bakir M et al (2017) Impact of high-dose oleuropein on cisplatin-induced oxidative stress, genotoxicity and pathological changes in rat stomach and lung. J Asian Nat Prod Res 19(12):1214–1231. https://doi.org/10.1080/10286020.2017

    Article  CAS  PubMed  Google Scholar 

  7. Türkdoğan MK, Akman N, Tuncer I, Uygan I, Kösem M, Özen S, Kara K, Bozkurt S, Memik F (2005) Epidemiological aspects of endemic upper gastrointestinal cancers in Eastern Turkey. Hepatogastroenterology 52(62):496–500.

    PubMed  Google Scholar 

  8. Ilic M, Ilic I (2022) Epidemiology of stomach cancer. World J Gastroenterol 28(12):1187–1203. https://doi.org/10.3748/wjg.v28.i12.1187

    Article  PubMed  PubMed Central  Google Scholar 

  9. Singh NP, McCoy MT, Tice RR, Schneider EL (1988) A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res 175(1):184–191. https://doi.org/10.1016/0014-4827(88)90265-0

    Article  CAS  PubMed  Google Scholar 

  10. Hartmann A, Agurell E, Beevers C, Brendler-Schwaab S, Burlinson B, Clay P et al (2003) Recommendations for conducting the in vivo alkaline Comet assay. Mutagenesis 18(1):45–51. https://doi.org/10.1093/mutage/18.1.45

    Article  CAS  PubMed  Google Scholar 

  11. Psaltopoulou T, Kosti RI, Haidopoulos D, Dimopoulos M, Panagiotakos DB (2011) Olive oil intake is inversely related to cancer prevalence: a systematic review and a meta-analysis of 13800 patients and 23340 controls in 19 observational studies. Lipids Health Dis 10(1):1–16. https://doi.org/10.1186/1476-511X-10-127

    Article  CAS  Google Scholar 

  12. Buiatti E, Palli D, Decarli A, Amadori D, Avellini C, Bianchi S et al (1990) A case-control study of gastric cancer and diet in Italy: II. Association with nutrients. Int J Cancer 45:896–901. https://doi.org/10.1002/ijc.2910440409

    Article  CAS  PubMed  Google Scholar 

  13. Palli D, Russo A, Ottini L, Masala G, Saieva C, Amorosi A et al (2001) Red meat, family history, and increased risk of gastric cancer with microsatellite instability. Cancer Res 61(14):5415–5419.

    CAS  PubMed  Google Scholar 

  14. Stoneham M, Goldacre M, Seagroatt V, Gill L (2000) Olive oil, diet and colorectal cancer: an ecological study and a hypothesis. J Epidemiol Community Health 54(10):756–760. https://doi.org/10.1136/jech.54.10.756

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Ahmad Farooqi A, Fayyaz S, Silva AS, Sureda A, Nabavi SF, Mocan A et al (2017) Oleuropein and cancer chemoprevention: the link is hot. Molecules 22(5):705. https://doi.org/10.3390/molecules22050705

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Imran M, Nadeem M, Gilani SA, Khan S, Sajid MW, Amir RM (2018) Antitumor perspectives of oleuropein and its metabolite hydroxytyrosol: recent updates. J Food Sci 83(7):1781–1791. https://doi.org/10.1111/1750-3841.14198

    Article  CAS  PubMed  Google Scholar 

  17. Khan M, Maryam A, Qazi JI, Ma T (2017) Olive Oil: an Angel of Protection Against Cancer. Adv Cancer Diet : 1–57.

  18. Galeone C, Talamini R, Levi F, Pelucchi C, Negri E, Giacosa A et al (2007) Fried foods, olive oil and colorectal cancer. Ann Oncol 18(1):36–39. https://doi.org/10.1093/annonc/mdl328

    Article  CAS  PubMed  Google Scholar 

  19. Gill CI, Boyd A, McDermott E, McCann M, Servili M, Selvaggini R et al (2005) Potential anti-cancer effects of virgin olive oil phenolson colorectal carcinogenesis models in vitro. Int J Cancer 117(1):1–7. https://doi.org/10.1002/ijc.21083

    Article  CAS  PubMed  Google Scholar 

  20. Llor X, Pons E, Roca A, Alvarez M, Mane J, Fernandez-Banares F et al (2003) The effects of fish oil, olive oil, oleic acid and linoleic acid on colorectal neoplastic processes. Clin Nutr 22(1):71–79. https://doi.org/10.1054/clnu.2002.0627

    Article  CAS  PubMed  Google Scholar 

  21. Giner E, Recio MC, Ríos JL, Cerdá-Nicolás JM, Giner RM (2016) Chemopreventive effect of oleuropein in colitis‐associated colorectal cancer in c57bl/6 mice. Mol Nutr Food Res 60(2):242–255. https://doi.org/10.1002/mnfr.201500605

    Article  CAS  PubMed  Google Scholar 

  22. Cheng JS, Chou CT, Liu YY, Sun WC, Shieh P, Kuo,D.H., et al (2016) The effect of oleuropein from olive leaf (Olea europaea) extract on Ca2 + homeostasis, cytotoxicity, cell cycle distribution and ROS signaling in HepG2 human hepatoma cells. Food Chem Toxicol 91:151–166. https://doi.org/10.1016/j.fct.2016.03.015

    Article  CAS  PubMed  Google Scholar 

  23. Yan CM, Chai EQ, Cai HY, Miao GY, Ma W (2015) Oleuropein induces apoptosis via activation of caspases and suppression of phosphatidylinositol 3-kinase/protein kinase B pathway in HepG2 human hepatoma cell line. Mol Med Rep 11(6):4617–4624. https://doi.org/10.3892/mmr.2015.3266

    Article  CAS  PubMed  Google Scholar 

  24. Goldsmith CD, Bond DR, Jankowski H, Weidenhofer J, Stathopoulos CE, Roach PD et al (2018) The olive biophenols oleuropein and hydroxytyrosol selectively reduce proliferation, influence the cell cycle, and induce apoptosis in pancreatic cancer cells. Int J M Olecular Sci 19(7):1937–1953. https://doi.org/10.3390/ijms19071937

    Article  CAS  Google Scholar 

  25. Acquaviva R, Di Giacomo C, Sorrenti V, Galvano F, Santangelo R, Cardile V et al (2012) Antiproliferative effect of oleuropein in prostate cell lines. Int J Oncol 41(1):31–38. https://doi.org/10.3892/ijo.2012

    Article  CAS  PubMed  Google Scholar 

  26. Samara P, Christoforidou N, Lemus C, Argyropoulou A, Ioannou K, Vougogiannopoulou K et al (2017) New semi-synthetic analogs of oleuropein show improved anticancer activity in vitro and in vivo. Eur J Med Chem 137:11–29. https://doi.org/10.1016/j.ejmech.2017.05.029

    Article  CAS  PubMed  Google Scholar 

  27. Hamdi HK, Castellon R (2005) Oleuropein, a non-toxic olive iridoid, is an anti-tumor agent and cytoskeleton disruptor. Biochem Biophys Res Commun 334(3):769–778. https://doi.org/10.1016/j.bbrc.2005.06.161

    Article  CAS  PubMed  Google Scholar 

  28. Barzegar F, Zaefizadeh M, Yari R, Salehzadeh A (2019) Synthesis of nano-paramagnetic oleuropein to induce KRAS over-expression: a new mechanism to inhibit AGS cancer cells. Medicina 55(7):388. https://doi.org/10.3390/medicina55070388

    Article  PubMed  PubMed Central  Google Scholar 

  29. Antognelli C, Frosini R, Santolla MF, Peirce MJ, Talesa VN (2019) Oleuropein-induced apoptosis is mediated by mitochondrial glyoxalase 2 in NSCLC A549 cells: a mechanistic inside and a possible novel nonenzymatic role for an ancient enzyme. Oxidative medicine and cellular longevity. 1–10. https://doi.org/10.1155/2019/8576961

  30. Liu L, Ahn KS, Shanmugam MK, Wang H, Shen H, Arfuso F et al (2019) Oleuropein induces apoptosis via abrogating NF-κB activation cascade in estrogen receptor–negative breast cancer cells. J Cell Biochem 120(3):4504–4513. https://doi.org/10.1002/jcb.27738

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This work was supported by the Bezmialem Vakif University Faculty of Medicine Scientific Research Project Fund (project number: 3.2014/35).

Author information

Authors and Affiliations

  1. Department of Nutrition and Dietetics, Faculty of Health Sciences, Istanbul Sabahattin Zaim University, Istanbul, Turkey

    Mehmed Kürşad Türkdoğan & Kübra Demir

  2. Department of Biochemistry, Medical Faculty, Bezmialem Vakif University, Istanbul, Turkey

    Abdurrahim Koçyiğit & Ömer Faruk Özer

  3. Department of Medical Biochemistry, Hamidiye School of Medicine, University of Health Sciences, Istanbul, Turkey

    Eray Metin Güler

  4. Department of Nutrition and Dietetics, Faculty of Health Sciences, İstanbul Medeniyet University, Istanbul, Turkey

    Halime Uğur

Authors
  1. Mehmed Kürşad Türkdoğan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Abdurrahim Koçyiğit
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Eray Metin Güler
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ömer Faruk Özer
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kübra Demir
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Halime Uğur
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

M.Kürşad Türkdoğan and Abdürrahim Koçyiğit contributed to the study conception and design. Material preparation and data collection were performed by Abdürrahim Koçyiğit, Eray Metin Güler. Data analysis were performed by M.Kürşad Türkdoğan, Abdürrahim Koçyiğit. The first draft of the manuscript was written by M. Kürşad Türkdoğan and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Mehmed Kürşad Türkdoğan.

Ethics declarations

Competing interests

“The authors have no relevant financial or non-financial interests to disclose.”

Ethics approval

This study was performed in line with the principles of the Declaration of Helsinki. No ethical approval is required since this is a cell culture study.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Türkdoğan, M.K., Koçyiğit, A., Güler, E.M. et al. Oleuropein exhibits anticarcinogen effects against gastric cancer cell lines. Mol Biol Rep 50, 9099–9105 (2023). https://doi.org/10.1007/s11033-023-08773-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-023-08773-y

Keywords

Search

Navigation