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@article{1726930,
author = {Kubatka, P. and Uramova, S. and Kello, M. and Kajo, K. and Samec, M. and Jasek, K. and Vybohova, D. and Liskova, A. and Mojzis, J. and Adamkov, M. and Zubor, P. and Šmejkal, Karel and Švajdlenka, Emil and Solar, P. and SM, Samuel and Zulli, A. and Kassayova, M. and Lasabova, Z. and Kwon, T.K. and Pec, M. and Danko, J. and Busselberg, D.},
article_location = {Basel, Switzerland},
article_number = {7},
doi = {http://dx.doi.org/10.3390/ijms20071749},
keywords = {angiogenesis; apoptosis; cancer stem cells; cell proliferation; epigenetics; mammary carcinogenesis; MCF-7 cells; MDA-MB-231 cells; predictive and preventive medicine; rat; Thymus vulgaris},
language = {eng},
issn = {1422-0067},
journal = {International Journal of Molecular Sciences},
title = {Anticancer Activities of Thymus vulgaris L. in Experimental Breast Carcinoma In Vivo and In Vitro},
volume = {20},
year = {2019}
}
TY - JOUR
ID - 1726930
AU - Kubatka, P. - Uramova, S. - Kello, M. - Kajo, K. - Samec, M. - Jasek, K. - Vybohova, D. - Liskova, A. - Mojzis, J. - Adamkov, M. - Zubor, P. - Šmejkal, Karel - Švajdlenka, Emil - Solar, P. - SM, Samuel - Zulli, A. - Kassayova, M. - Lasabova, Z. - Kwon, T.K. - Pec, M. - Danko, J. - Busselberg, D.
PY - 2019
TI - Anticancer Activities of Thymus vulgaris L. in Experimental Breast Carcinoma In Vivo and In Vitro
JF - International Journal of Molecular Sciences
VL - 20
IS - 7
PB - MDPI AG
SN - 14220067
KW - angiogenesis
KW - apoptosis
KW - cancer stem cells
KW - cell proliferation
KW - epigenetics
KW - mammary carcinogenesis
KW - MCF-7 cells
KW - MDA-MB-231 cells
KW - predictive and preventive medicine
KW - rat
KW - Thymus vulgaris
N2 - Naturally-occurring mixtures of phytochemicals present in plant foods are proposed to possess tumor-suppressive activities. In this work, we aimed to evaluate the antitumor effects of Thymus vulgaris L. in in vivo and in vitro mammary carcinoma models. Dried T. vulgaris (as haulm) was continuously administered at two concentrations of 0.1% and 1% in the diet in a chemically-induced rat mammary carcinomas model and a syngeneic 4T1 mouse model. After autopsy, histopathological and molecular analyses of rodent mammary carcinomas were performed. In addition, in vitro evaluations using MCF-7 and MDA-MB-231 cells were carried out. In mice, T. vulgaris at both doses reduced the volume of 4T1 tumors by 85% (0.1%) and 84% (1%) compared to the control, respectively. Moreover, treated tumors showed a substantial decrease in necrosis/tumor area ratio and mitotic activity index. In the rat model, T. vulgaris (1%) decreased the tumor frequency by 53% compared to the control. Analysis of the mechanisms of anticancer action included well-described and validated diagnostic and prognostic markers that are used in both clinical approach and preclinical research. In this regard, the analyses of treated rat carcinoma cells showed a CD44 and ALDH1A1 expression decrease and Bax expression increase. Malondialdehyde (MDA) levels and VEGFR-2 expression were decreased in rat carcinomas in both the T. vulgaris treated groups. Regarding the evaluations of epigenetic changes in rat tumors, we found a decrease in the lysine methylation status of H3K4me3 in both treated groups (H3K9m3, H4K20m3, and H4K16ac were not changed); up-regulations of miR22, miR34a, and miR210 expressions (only at higher doses); and significant reductions in the methylation status of four gene promoters-ATM serin/threonine kinase, also known as the NPAT gene (ATM); Ras-association domain family 1, isoform A (RASSF1); phosphatase and tensin homolog (PTEN); and tissue inhibitor of metalloproteinase-3 (TIMP3) (the paired-like homeodomain transcription factor (PITX2) promoter was not changed). In vitro study revealed the antiproliferative and proapoptotic effects of essential oils of T. vulgaris in MCF-7 and MDA-MB-231 cells (analyses of 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) (MTS); 5-bromo-20-deoxyuridine (BrdU); cell cycle; annexin V/PI; caspase-3/7; Bcl-2; PARP; and mitochondrial membrane potential). T. vulgaris L. demonstrated significant chemopreventive and therapeutic activities against experimental breast carcinoma.
ER -
KUBATKA, P., S. URAMOVA, M. KELLO, K. KAJO, M. SAMEC, K. JASEK, D. VYBOHOVA, A. LISKOVA, J. MOJZIS, M. ADAMKOV, P. ZUBOR, Karel ŠMEJKAL, Emil ŠVAJDLENKA, P. SOLAR, Samuel SM, A. ZULLI, M. KASSAYOVA, Z. LASABOVA, T.K. KWON, M. PEC, J. DANKO and D. BUSSELBERG. Anticancer Activities of Thymus vulgaris L. in Experimental Breast Carcinoma In Vivo and In Vitro. \textit{International Journal of Molecular Sciences}. Basel, Switzerland: MDPI AG, 2019, vol.~20, No~7, 29 pp. ISSN~1422-0067. Available from: https://dx.doi.org/10.3390/ijms20071749.
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