Chemopreventive and Therapeutic Efficacy of Cinnamomum
zeylanicum L. Bark in Experimental Breast Carcinoma:
Mechanistic In Vivo and In Vitro Analyses

J 2020

Chemopreventive and Therapeutic Efficacy of Cinnamomum zeylanicum L. Bark in Experimental Breast Carcinoma: Mechanistic In Vivo and In Vitro Analyses

KUBATKA, P., M. KELLO, K. KAJO, M. SAMEC, K. JASEK et. al.

Základní údaje

Originální název

Chemopreventive and Therapeutic Efficacy of Cinnamomum zeylanicum L. Bark in Experimental Breast Carcinoma: Mechanistic In Vivo and In Vitro Analyses

Autoři

KUBATKA, P., M. KELLO, K. KAJO, M. SAMEC, K. JASEK, D. VYBOHOVA, S. URAMOVA, A. LISKOVA, V. SADLONOVA, L. KOKLESOVA, R. MURIN, M. ADAMKOV, Karel ŠMEJKAL (203 Česká republika, domácí), Emil ŠVAJDLENKA (203 Česká republika, domácí), P. SOLAR, S. M. SAMUEL, M. KASSAYOVA, T. K. KWON, P. ZUBOR, M. PEC, J. DANKO, D. BUSSELBERG a J. MOJZIS

Vydání

Molecules, Basel, MDPI, 2020, 1079-9796

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30104 Pharmacology and pharmacy

Stát vydavatele

Švýcarsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 3.039

Kód RIV

RIV/00216224:14160/20:00118237

Organizační jednotka

Farmaceutická fakulta

DOI

http://dx.doi.org/10.3390/molecules25061399

UT WoS

000530248700142

Klíčová slova anglicky

apoptosis; cancer stem cells; cell proliferation; Cinnamomum zeylanicum; epigenetics; mammary carcinogenesis; MCF-7 cells; MDA-MB-231 cells; mouse; preventive medicine; rat

Štítky

rivok, ÚPL

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 24. 2. 2021 13:18, Mgr. Hana Hurtová

Anotace

V originále

Comprehensive oncology research suggests an important role of phytochemicals or whole plant foods in the modulation of signaling pathways associated with anticancer action. The goal of this study is to assess the anticancer activities of Cinnamomum zeylanicum L. using rat, mouse, and cell line breast carcinoma models. C. zeylanicum (as bark powder) was administered in the diet at two concentrations of 0.1% (w/w) and 1% (w/w) during the whole experiment in chemically induced rat mammary carcinomas and a syngeneic 4T1 mouse model. After autopsy, histopathological and molecular evaluations of mammary gland tumors in rodents were carried out. Moreover, in vitro analyses using MCF-7 and MDA-MB-231 cells were performed. The dominant metabolites present in the tested C. zeylanicum essential oil (with relative content over 1%) were cinnamaldehyde, cinnamaldehyde dimethyl acetal, cinnamyl acetate, eugenol, linalool, eucalyptol, limonene, o-cymol, and alpha -terpineol. The natural mixture of mentioned molecules demonstrated significant anticancer effects in our study. In the mouse model, C. zeylanicum at a higher dose (1%) significantly decreased tumor volume by 44% when compared to controls. In addition, treated tumors showed a significant dose-dependent decrease in mitotic activity index by 29% (0.1%) and 45.5% (1%) in comparison with the control group. In rats, C. zeylanicum in both doses significantly reduced the tumor incidence by 15.5% and non-significantly suppressed tumor frequency by more than 30% when compared to controls. An evaluation of the mechanism of anticancer action using valid oncological markers showed several positive changes after treatment with C. zeylanicum. Histopathological analysis of treated rat tumor specimens showed a significant decrease in the ratio of high-/low-grade carcinomas compared to controls. In treated rat carcinomas, we found caspase-3 and Bax expression increase. On the other hand, we observed a decrease in Bcl-2, Ki67, VEGF, and CD24 expressions and MDA levels. Assessment of epigenetic changes in rat tumor cells in vivo showed a significant decrease in lysine methylation status of H3K4m3 and H3K9m3 in the high-dose treated group, a dose-dependent increase in H4K16ac levels (H4K20m3 was not changed), down-regulations of miR21 and miR155 in low-dose cinnamon groups (miR22 and miR34a were not modulated), and significant reduction of the methylation status of two out of five gene promoters-ATM and TIMP3 (PITX2, RASSF1, PTEN promoters were not changed). In vitro study confirmed results of animal studies, in that the essential oil of C. zeylanicum displayed significant anticancer efficacy in MCF-7 and MDA-MB-231 cells (using MTS, BrdU, cell cycle, annexin V/PI, caspase-3/7, Bcl-2, PARP, and mitochondrial membrane potential analyses). As a conclusion, C. zeylanicum L. showed chemopreventive and therapeutic activities in animal breast carcinoma models that were also significantly confirmed by mechanistic evaluations in vitro and in vivo.

Citovat

KUBATKA, P., M. KELLO, K. KAJO, M. SAMEC, K. JASEK, D. VYBOHOVA, S. URAMOVA, A. LISKOVA, V. SADLONOVA, L. KOKLESOVA, R. MURIN, M. ADAMKOV, Karel ŠMEJKAL, Emil ŠVAJDLENKA, P. SOLAR, S. M. SAMUEL, M. KASSAYOVA, T. K. KWON, P. ZUBOR, M. PEC, J. DANKO, D. BUSSELBERG a J. MOJZIS. Chemopreventive and Therapeutic Efficacy of Cinnamomum zeylanicum L. Bark in Experimental Breast Carcinoma: Mechanistic In Vivo and In Vitro Analyses. Molecules. Basel: MDPI, 2020, roč. 25, č. 6, s. 1-32. ISSN 1079-9796. Dostupné z: https://dx.doi.org/10.3390/molecules25061399.

@article{1745259,
   author = {Kubatka, P. and Kello, M. and Kajo, K. and Samec, M. and Jasek, K. and Vybohova, D. and Uramova, S. and Liskova, A. and Sadlonova, V. and Koklesova, L. and Murin, R. and Adamkov, M. and Šmejkal, Karel and Švajdlenka, Emil and Solar, P. and Samuel, S. M. and Kassayova, M. and Kwon, T. K. and Zubor, P. and Pec, M. and Danko, J. and Busselberg, D. and Mojzis, J.},
   article_location = {Basel},
   article_number = {6},
   doi = {http://dx.doi.org/10.3390/molecules25061399},
   keywords = {apoptosis; cancer stem cells; cell proliferation; Cinnamomum zeylanicum; epigenetics; mammary carcinogenesis; MCF-7 cells; MDA-MB-231 cells; mouse; preventive medicine; rat},
   language = {eng},
   issn = {1079-9796},
   journal = {Molecules},
   title = {Chemopreventive and Therapeutic Efficacy of Cinnamomum zeylanicum L. Bark in Experimental Breast Carcinoma: Mechanistic In Vivo and In Vitro Analyses},
   url = {https://pubmed.ncbi.nlm.nih.gov/32204409/},
   volume = {25},
   year = {2020}
}

TY  - JOUR
ID  - 1745259
AU  - Kubatka, P. - Kello, M. - Kajo, K. - Samec, M. - Jasek, K. - Vybohova, D. - Uramova, S. - Liskova, A. - Sadlonova, V. - Koklesova, L. - Murin, R. - Adamkov, M. - Šmejkal, Karel - Švajdlenka, Emil - Solar, P. - Samuel, S. M. - Kassayova, M. - Kwon, T. K. - Zubor, P. - Pec, M. - Danko, J. - Busselberg, D. - Mojzis, J.
PY  - 2020
TI  - Chemopreventive and Therapeutic Efficacy of Cinnamomum zeylanicum L. Bark in Experimental Breast Carcinoma: Mechanistic In Vivo and In Vitro Analyses
JF  - Molecules
VL  - 25
IS  - 6
SP  - 1-32
EP  - 1-32
PB  - MDPI
SN  - 10799796
KW  - apoptosis
KW  - cancer stem cells
KW  - cell proliferation
KW  - Cinnamomum zeylanicum
KW  - epigenetics
KW  - mammary carcinogenesis
KW  - MCF-7 cells
KW  - MDA-MB-231 cells
KW  - mouse
KW  - preventive medicine
KW  - rat
UR  - https://pubmed.ncbi.nlm.nih.gov/32204409/
N2  - Comprehensive oncology research suggests an important role of phytochemicals or whole plant foods in the modulation of signaling pathways associated with anticancer action. The goal of this study is to assess the anticancer activities of Cinnamomum zeylanicum L. using rat, mouse, and cell line breast carcinoma models. C. zeylanicum (as bark powder) was administered in the diet at two concentrations of 0.1% (w/w) and 1% (w/w) during the whole experiment in chemically induced rat mammary carcinomas and a syngeneic 4T1 mouse model. After autopsy, histopathological and molecular evaluations of mammary gland tumors in rodents were carried out. Moreover, in vitro analyses using MCF-7 and MDA-MB-231 cells were performed. The dominant metabolites present in the tested C. zeylanicum essential oil (with relative content over 1%) were cinnamaldehyde, cinnamaldehyde dimethyl acetal, cinnamyl acetate, eugenol, linalool, eucalyptol, limonene, o-cymol, and alpha -terpineol. The natural mixture of mentioned molecules demonstrated significant anticancer effects in our study. In the mouse model, C. zeylanicum at a higher dose (1%) significantly decreased tumor volume by 44% when compared to controls. In addition, treated tumors showed a significant dose-dependent decrease in mitotic activity index by 29% (0.1%) and 45.5% (1%) in comparison with the control group. In rats, C. zeylanicum in both doses significantly reduced the tumor incidence by 15.5% and non-significantly suppressed tumor frequency by more than 30% when compared to controls. An evaluation of the mechanism of anticancer action using valid oncological markers showed several positive changes after treatment with C. zeylanicum. Histopathological analysis of treated rat tumor specimens showed a significant decrease in the ratio of high-/low-grade carcinomas compared to controls. In treated rat carcinomas, we found caspase-3 and Bax expression increase. On the other hand, we observed a decrease in Bcl-2, Ki67, VEGF, and CD24 expressions and MDA levels. Assessment of epigenetic changes in rat tumor cells in vivo showed a significant decrease in lysine methylation status of H3K4m3 and H3K9m3 in the high-dose treated group, a dose-dependent increase in H4K16ac levels (H4K20m3 was not changed), down-regulations of miR21 and miR155 in low-dose cinnamon groups (miR22 and miR34a were not modulated), and significant reduction of the methylation status of two out of five gene promoters-ATM and TIMP3 (PITX2, RASSF1, PTEN promoters were not changed). In vitro study confirmed results of animal studies, in that the essential oil of C. zeylanicum displayed significant anticancer efficacy in MCF-7 and MDA-MB-231 cells (using MTS, BrdU, cell cycle, annexin V/PI, caspase-3/7, Bcl-2, PARP, and mitochondrial membrane potential analyses). As a conclusion, C. zeylanicum L. showed chemopreventive and therapeutic activities in animal breast carcinoma models that were also significantly confirmed by mechanistic evaluations in vitro and in vivo.
ER  -

KUBATKA, P., M. KELLO, K. KAJO, M. SAMEC, K. JASEK, D. VYBOHOVA, S. URAMOVA, A. LISKOVA, V. SADLONOVA, L. KOKLESOVA, R. MURIN, M. ADAMKOV, Karel ŠMEJKAL, Emil ŠVAJDLENKA, P. SOLAR, S. M. SAMUEL, M. KASSAYOVA, T. K. KWON, P. ZUBOR, M. PEC, J. DANKO, D. BUSSELBERG a J. MOJZIS. Chemopreventive and Therapeutic Efficacy of Cinnamomum zeylanicum L. Bark in Experimental Breast Carcinoma: Mechanistic In Vivo and In Vitro Analyses. \textit{Molecules}. Basel: MDPI, 2020, roč.~25, č.~6, s.~1-32. ISSN~1079-9796. Dostupné z: https://dx.doi.org/10.3390/molecules25061399.

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