Oregano demonstrates distinct tumour-suppressive effects in the breast carcinoma model
- 260 Downloads
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.
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.
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.
Our results demonstrate, for the first time, a distinct tumour-suppressive effect of oregano in the breast cancer model.
KeywordsMammary carcinogenesis Rat Oregano Cancer stem cells Angiogenesis Apoptosis Cell proliferation MCF-7 cells
Cancer stem cells
Flow cytometry analysis
Epithelial cellular adhesion molecule
Limit of quantification
Human adenocarcinoma cell line, oestrogen receptor positive
- ORE 0.3/ORE 3
Experimental group with dietary administered oregano in a concentration of 0.3 and 3 %
Vascular endothelial growth factor
Vascular endothelial growth factor receptor-2
Very low-density lipoprotein
- 18.Ito M, Shien T, Omori M, Mizoo T, Iwamoto T, Nogami T et al (2015) Evaluation of aldehyde dehydrogenase 1 and transcription factors in both primary breast cancer and axillary lymph node metastases as a prognostic factor. Breast Cancer [Epub ahead of print]Google Scholar
- 20.Chekhun SV, Zadvorny TV, Tymovska YO, Anikusko MF, Novak OE, Polishchuk LZ (2015) CD44+/CD24− markers of cancer stem cells in patients with breast cancer of different molecular subtypes. Exp Oncol 37:58–63Google Scholar
- 23.Gottardis MM, Jordan VC (1987) Antitumor actions of keoxifene and tamoxifen in the N-nitrosomethylurea-induced rat mammary carcinoma model. Cancer Res 47:4020–4024Google Scholar
- 26.Kubatka P, Kapinová A, Kello M, Kruzliak P, Kajo K, Výbohová D et al (2015) Fruit peel polyphenols demonstrate substantial anti-tumour effects in the model of breast cancer. Eur J Nutr [Epub ahead of print]Google Scholar
- 27.Mylona E, Nomikos A, Alexandrou P, Giannopoulou I, Keramopoulos A, Nakopoulou L (2007) Lymphatic and blood vessel morphometry in invasive breast carcinomas: relation with proliferation and VEGF-C and -D proteins expression. Histol Histopathol 22:825–835Google Scholar
- 38.Kim JA, Kim DH, Hossain MA, Kim MY, Sung B, Yoon JH et al (2014) HS-1793, a resveratrol analogue, induces cell cycle arrest and apoptotic cell death in human breast cancer cells. Int J Oncol 44:473–480Google Scholar
- 42.Dean M (2005) Cancer stem cells: implications for cancer causation and therapy resistance. Discov Med 5:278–282Google Scholar
- 46.Ouhtit A, Gaur RL, Abdraboh M, Ireland SK, Rao PN, Raj SG et al (2013) Simultaneous inhibition of cell-cycle, proliferation, survival, metastatic pathways and induction of apoptosis in breast cancer cells by a phytochemical super-cocktail: genes that underpin its mode of action. J Cancer 4:703–715CrossRefGoogle Scholar