title: Oregano demonstrates distinct tumour-suppressive effects in the breast carcinoma model.
abstract: OBJECTIVE
  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/G1DNA 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.
authors.affiliation: Department of Medical Biology, Jessenius Faculty of Medicine, Comenius University in Bratislava, Malá Hora 4, 03601, Martin, Slovakia. kubatkap@gmail.com.
authors.forename: Peter
authors.initials: P
authors.lastname: Kubatka
authors.affiliation: Department of Pharmacology, Faculty of Medicine, P. J. Šafárik University, Kosice, Slovakia.
authors.forename: Martin
authors.initials: M
authors.lastname: Kello
authors.affiliation: Department of Pathology, Slovak Medical University and St. Elisabeth Oncology Institute, Bratislava, Slovakia.
authors.forename: Karol
authors.initials: K
authors.lastname: Kajo
authors.affiliation: 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. kruzliakpeter@gmail.com.
authors.forename: Peter
authors.initials: P
authors.lastname: Kruzliak
authors.affiliation: Department of Anatomy, Jessenius Faculty of Medicine, Comenius University in Bratislava, Martin, Slovakia.
authors.forename: Desanka
authors.initials: D
authors.lastname: Výbohová
authors.affiliation: Department of Pharmacology, Faculty of Medicine, P. J. Šafárik University, Kosice, Slovakia.
authors.forename: Ján
authors.initials: J
authors.lastname: Mojžiš
authors.affiliation: Department of Histology and Embryology, Jessenius Faculty of Medicine, Comenius University in Bratislava, Martin, Slovakia.
authors.forename: Marián
authors.initials: M
authors.lastname: Adamkov
authors.affiliation: Department of Pharmacognosy and Botany, Faculty of Pharmacy, Comenius University in Bratislava, Bratislava, Slovakia.
authors.forename: Silvia
authors.initials: S
authors.lastname: Fialová
authors.affiliation: Department of Pharmaceutical Analysis and Nuclear Pharmacy, Faculty of Pharmacy, Toxicological and Antidoping Center, Comenius University in Bratislava, Bratislava, Slovakia.
authors.forename: Lucia
authors.initials: L
authors.lastname: Veizerová
authors.affiliation: The Centre for Chronic Disease Prevention and Management (CCDPM), College of Health and Biomedicine, Victoria University, Melbourne, VIC, Australia.
authors.forename: Anthony
authors.initials: A
authors.lastname: Zulli
authors.affiliation: Department of Medical Biology, Jessenius Faculty of Medicine, Comenius University in Bratislava, Malá Hora 4, 03601, Martin, Slovakia. pec@jfmed.uniba.sk.
authors.forename: Martin
authors.initials: M
authors.lastname: Péč
authors.affiliation: Clinic of Stomatology and Maxillofacial Surgery, Jessenius Faculty of Medicine, Comenius University in Bratislava, Martin, Slovakia.
authors.forename: Dagmar
authors.initials: D
authors.lastname: Statelová
authors.affiliation: Department of Pharmacognosy and Botany, Faculty of Pharmacy, Comenius University in Bratislava, Bratislava, Slovakia.
authors.forename: Daniel
authors.initials: D
authors.lastname: Grančai
authors.affiliation: Department of Physiology and Biophysics, Weill Cornell Medical College in Qatar, Qatar Foundation - Education City, Doha, Qatar.
authors.forename: Dietrich
authors.initials: D
authors.lastname: Büsselberg
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy*; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D005612:Freeze Drying; D006801:Humans; D061986:MCF-7 Cells; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D031341:Origanum / Q000737:chemistry*; D008517:Phytotherapy; D028321:Plant Preparations / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D028321:Plant Preparations
keywords: Angiogenesis; Apoptosis; Cancer stem cells; Cell proliferation; MCF-7 cells; Mammary carcinogenesis; Oregano; Rat