European Journal of Nutrition

, Volume 56, Issue 3, pp 1303–1316 | Cite as

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

  • Peter Kubatka
  • Martin Kello
  • Karol Kajo
  • Peter Kruzliak
  • Desanka Výbohová
  • Ján Mojžiš
  • Marián Adamkov
  • Silvia Fialová
  • Lucia Veizerová
  • Anthony Zulli
  • Martin Péč
  • Dagmar Statelová
  • Daniel Grančai
  • Dietrich Büsselberg
Original Contribution

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-G0/G1 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.

Keywords

Mammary carcinogenesis Rat Oregano Cancer stem cells Angiogenesis Apoptosis Cell proliferation MCF-7 cells 

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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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Peter Kubatka
    • 1
  • Martin Kello
    • 2
  • Karol Kajo
    • 3
  • Peter Kruzliak
    • 4
  • Desanka Výbohová
    • 5
  • Ján Mojžiš
    • 2
  • Marián Adamkov
    • 6
  • Silvia Fialová
    • 7
  • Lucia Veizerová
    • 8
  • Anthony Zulli
    • 9
  • Martin Péč
    • 1
  • Dagmar Statelová
    • 10
  • Daniel Grančai
    • 7
  • Dietrich Büsselberg
    • 11
  1. 1.Department of Medical Biology, Jessenius Faculty of MedicineComenius University in BratislavaMartinSlovakia
  2. 2.Department of Pharmacology, Faculty of MedicineP. J. Šafárik UniversityKosiceSlovakia
  3. 3.Department of PathologySlovak Medical University and St. Elisabeth Oncology InstituteBratislavaSlovakia
  4. 4.Laboratory of Structural Biology and Proteomics, Central LaboratoriesFaculty of Pharmacy, University of Veterinary and Pharmaceutical SciencesBrnoCzech Republic
  5. 5.Department of Anatomy, Jessenius Faculty of MedicineComenius University in BratislavaMartinSlovakia
  6. 6.Department of Histology and Embryology, Jessenius Faculty of MedicineComenius University in BratislavaMartinSlovakia
  7. 7.Department of Pharmacognosy and Botany, Faculty of PharmacyComenius University in BratislavaBratislavaSlovakia
  8. 8.Department of Pharmaceutical Analysis and Nuclear Pharmacy, Faculty of Pharmacy, Toxicological and Antidoping CenterComenius University in BratislavaBratislavaSlovakia
  9. 9.The Centre for Chronic Disease Prevention and Management (CCDPM), College of Health and BiomedicineVictoria UniversityMelbourneAustralia
  10. 10.Clinic of Stomatology and Maxillofacial Surgery, Jessenius Faculty of MedicineComenius University in BratislavaMartinSlovakia
  11. 11.Department of Physiology and Biophysics, Weill Cornell Medical College in QatarQatar Foundation – Education CityDohaQatar

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