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Oregano demonstrates distinct tumour-suppressive effects in the breast carcinoma model

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Abstract

Purpose

There has been a considerable interest in the identification of natural plant foods for developing effective agents against cancer. Thus, the anti-tumour effects of oregano in the in vivo and in vitro breast cancer model were evaluated.

Methods

Lyophilized oregano (ORE) was administered at two concentrations of 0.3 and 3 % through diet. The experiment was terminated 14 weeks after carcinogen administration. At autopsy, mammary tumours were removed and prepared for histopathological and immunohistochemical analysis. Moreover, in vitro evaluation in MCF-7 cells was carried out.

Results

Low-dose ORE suppressed tumour frequency by 55.5 %, tumour incidence by 44 %, and tumour volume by 44.5 % compared to control animals. Analysis of rat tumour cells showed Ki67, VEGFR-2, CD24, and EpCAM expression decrease and caspase-3 expression increase after low-dose ORE treatment. High-dose ORE lengthened tumour latency by 12.5 days; moreover, Bcl-2, VEGFR-2, CD24, and EpCAM expression decrease and caspase-3 expression increase in carcinoma cells were observed. Histopathological analysis revealed a decrease in the ratio of high-/low-grade carcinomas in both treated groups. In vitro studies showed that ORE decreased survival and proliferation of MCF-7 cells. In ORE-treated MCF-7 cells, an increase in cells expressing sub-G 0/G 1 DNA content and an increase in the percentage of annexin V/PI positive MCF-7 cells were observed. In vitro, both caspase-dependent and possible non-caspase-dependent apoptotic pathways were found. The deactivation of anti-apoptotic activity of Bcl-2, a decrease in mitochondrial membrane potential, and the activation of mitochondrial apoptosis pathway were observed in the ORE-treated MCF-7 cells.

Conclusions

Our results demonstrate, for the first time, a distinct tumour-suppressive effect of oregano in the breast cancer model.

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Abbreviations

AIF:

Apoptosis-inducing factor

ALDH:

Aldehyde dehydrogenase

BrdU:

5-Bromo-20-deoxyuridine

CSCs:

Cancer stem cells

FCM:

Flow cytometry analysis

HDL:

High-density lipoprotein

HG:

High grade

EpCAM:

Epithelial cellular adhesion molecule

LDL:

Low-density lipoprotein

LG:

Low grade

LOQ:

Limit of quantification

MCF-7:

Human adenocarcinoma cell line, oestrogen receptor positive

NMU:

N-methyl-N-nitrosourea

ORE 0.3/ORE 3:

Experimental group with dietary administered oregano in a concentration of 0.3 and 3 %

ORE:

Oregano

VEGF:

Vascular endothelial growth factor

VEGFR-2:

Vascular endothelial growth factor receptor-2

VLDL:

Very low-density lipoprotein

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Acknowledgments

This work was supported by the Scientific Grant Agency of the Ministry of Education of the Slovak Republic under the Contract No. VEGA 1/0108/16 and 1/0290/16 and by the Slovak Research and Development Agency under the Contract Nos. APVV-0325-07 and APVV-0550-11. This work was supported by the Grant “Martin Biomedical Centre” (ITMS: 26220220187), “Competence center for research and development in diagnosis and therapy”, code: 26220220153, and the Grant FNUSA-ICRC (No. CZ.1.05/1.1.00/02.0123), both projects co-funded from EU sources and European Regional Development Fund. This study was also supported by the project Medicínsky univerzitný park v Košiciach (MediPark, Košice) ITMS:26220220185 supported by Operational Programme Research and Development (OP VaV-2012/2.2/08-RO) (Contract No. OPVaV/12/2013). We thank to Eva Jakubovičová, Agáta Rešetárová, and Margaréta Kondeková for technical support.

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Authors and Affiliations

  1. Department of Medical Biology, Jessenius Faculty of Medicine, Comenius University in Bratislava, Malá Hora 4, 03601, Martin, Slovakia

    Peter Kubatka & Martin Péč

  2. Department of Pharmacology, Faculty of Medicine, P. J. Šafárik University, Kosice, Slovakia

    Martin Kello & Ján Mojžiš

  3. Department of Pathology, Slovak Medical University and St. Elisabeth Oncology Institute, Bratislava, Slovakia

    Karol Kajo

  4. Laboratory of Structural Biology and Proteomics, Central Laboratories, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Palackeho tr. 1946/1, 612 42, Brno, Czech Republic

    Peter Kruzliak

  5. Department of Anatomy, Jessenius Faculty of Medicine, Comenius University in Bratislava, Martin, Slovakia

    Desanka Výbohová

  6. Department of Histology and Embryology, Jessenius Faculty of Medicine, Comenius University in Bratislava, Martin, Slovakia

    Marián Adamkov

  7. Department of Pharmacognosy and Botany, Faculty of Pharmacy, Comenius University in Bratislava, Bratislava, Slovakia

    Silvia Fialová & Daniel Grančai

  8. Department of Pharmaceutical Analysis and Nuclear Pharmacy, Faculty of Pharmacy, Toxicological and Antidoping Center, Comenius University in Bratislava, Bratislava, Slovakia

    Lucia Veizerová

  9. The Centre for Chronic Disease Prevention and Management (CCDPM), College of Health and Biomedicine, Victoria University, Melbourne, VIC, Australia

    Anthony Zulli

  10. Clinic of Stomatology and Maxillofacial Surgery, Jessenius Faculty of Medicine, Comenius University in Bratislava, Martin, Slovakia

    Dagmar Statelová

  11. Department of Physiology and Biophysics, Weill Cornell Medical College in Qatar, Qatar Foundation – Education City, Doha, Qatar

    Dietrich Büsselberg

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  1. Peter Kubatka
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  2. Martin Kello
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  3. Karol Kajo
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  14. Dietrich Büsselberg
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Correspondence to Peter Kubatka, Peter Kruzliak or Martin Péč.

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Kubatka, P., Kello, M., Kajo, K. et al. Oregano demonstrates distinct tumour-suppressive effects in the breast carcinoma model. Eur J Nutr 56, 1303–1316 (2017). https://doi.org/10.1007/s00394-016-1181-5

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  • DOI: https://doi.org/10.1007/s00394-016-1181-5

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