Peter Kubatka1, Martin Kello2, Karol Kajo3, Peter Kruzliak4, Desanka Výbohová5, Ján Mojžiš2, Marián Adamkov6, Silvia Fialová7, Lucia Veizerová8, Anthony Zulli9, Martin Péč10, Dagmar Statelová11, Daniel Grančai7, Dietrich Büsselberg12. 1. Department of Medical Biology, Jessenius Faculty of Medicine, Comenius University in Bratislava, Malá Hora 4, 03601, Martin, Slovakia. kubatkap@gmail.com. 2. Department of Pharmacology, Faculty of Medicine, P. J. Šafárik University, Kosice, Slovakia. 3. Department of Pathology, Slovak Medical University and St. Elisabeth Oncology Institute, Bratislava, Slovakia. 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. kruzliakpeter@gmail.com. 5. Department of Anatomy, Jessenius Faculty of Medicine, Comenius University in Bratislava, Martin, Slovakia. 6. Department of Histology and Embryology, Jessenius Faculty of Medicine, Comenius University in Bratislava, Martin, Slovakia. 7. Department of Pharmacognosy and Botany, Faculty of Pharmacy, Comenius University in Bratislava, Bratislava, Slovakia. 8. Department of Pharmaceutical Analysis and Nuclear Pharmacy, Faculty of Pharmacy, Toxicological and Antidoping Center, Comenius University in Bratislava, Bratislava, Slovakia. 9. The Centre for Chronic Disease Prevention and Management (CCDPM), College of Health and Biomedicine, Victoria University, Melbourne, VIC, Australia. 10. Department of Medical Biology, Jessenius Faculty of Medicine, Comenius University in Bratislava, Malá Hora 4, 03601, Martin, Slovakia. pec@jfmed.uniba.sk. 11. Clinic of Stomatology and Maxillofacial Surgery, Jessenius Faculty of Medicine, Comenius University in Bratislava, Martin, Slovakia. 12. Department of Physiology and Biophysics, Weill Cornell Medical College in Qatar, Qatar Foundation - Education City, Doha, Qatar.
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.
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 rattumour 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.
Entities:
Keywords:
Angiogenesis; Apoptosis; Cancer stem cells; Cell proliferation; MCF-7 cells; Mammary carcinogenesis; Oregano; Rat
Authors: Terézia Kisková; Rastislav Jendželovský; Erdenetsetsek Rentsen; Alexandra Maier-Salamon; Natália Kokošová; Zuzana Papčová; Jaromír Mikeš; Peter Orendáš; Bianka Bojková; Peter Kubatka; Martin Svoboda; Karol Kajo; Peter Fedoročko; Walter Jäger; Cem Ekmekcioglu; Monika Kassayová; Theresia Thalhammer Journal: Eur J Cancer Prev Date: 2014-11 Impact factor: 2.497
Authors: Thomas Klonisch; Emilia Wiechec; Sabine Hombach-Klonisch; Sudharsana R Ande; Sebastian Wesselborg; Klaus Schulze-Osthoff; Marek Los Journal: Trends Mol Med Date: 2008-09-03 Impact factor: 11.951
Authors: E Mylona; A Nomikos; P Alexandrou; I Giannopoulou; A Keramopoulos; L Nakopoulou Journal: Histol Histopathol Date: 2007-08 Impact factor: 2.303
Authors: Alena Liskova; Patrik Stefanicka; Marek Samec; Karel Smejkal; Pavol Zubor; Tibor Bielik; Kristina Biskupska-Bodova; Taeg Kyu Kwon; Jan Danko; Dietrich Büsselberg; Mariusz Adamek; Luis Rodrigo; Peter Kruzliak; Aleksandr Shleikin; Peter Kubatka Journal: Clin Exp Med Date: 2020-02-03 Impact factor: 3.984
Authors: Peter Kubatka; Sona Uramova; Martin Kello; Karol Kajo; Peter Kruzliak; Jan Mojzis; Desanka Vybohova; Marian Adamkov; Karina Jasek; Zora Lasabova; Pavol Zubor; Silvia Fialova; Svetlana Dokupilova; Peter Solar; Martin Pec; Katarina Adamicova; Jan Danko; Mariusz Adamek; Dietrich Busselberg Journal: J Cell Mol Med Date: 2017-05-19 Impact factor: 5.310
Authors: A Kapinova; P Kubatka; O Golubnitschaja; M Kello; P Zubor; P Solar; M Pec Journal: Environ Health Prev Med Date: 2018-08-09 Impact factor: 3.674
Authors: Lenka Koklesova; Alena Liskova; Marek Samec; Tawar Qaradakhi; Anthony Zulli; Karel Smejkal; Karol Kajo; Jana Jakubikova; Payam Behzadi; Martin Pec; Pavol Zubor; Kamil Biringer; Taeg Kyu Kwon; Dietrich Büsselberg; Gustavo R Sarria; Frank A Giordano; Olga Golubnitschaja; Peter Kubatka Journal: EPMA J Date: 2020-05-29 Impact factor: 6.543
Authors: Alena Liskova; Peter Kubatka; Marek Samec; Pavol Zubor; Milos Mlyncek; Tibor Bielik; Samson Mathews Samuel; Anthony Zulli; Taeg Kyu Kwon; Dietrich Büsselberg Journal: Molecules Date: 2019-03-04 Impact factor: 4.411