Rhus coriaria L. (Sumac) Demonstrates Oncostatic Activity in
the Therapeutic and Preventive Model of Breast Carcinoma

J 2021

Rhus coriaria L. (Sumac) Demonstrates Oncostatic Activity in the Therapeutic and Preventive Model of Breast Carcinoma

KUBATKA, P., M. KELLO, K. KAJO, M. SAMEC, A. LISKOVA et. al.

Basic information

Original name

Rhus coriaria L. (Sumac) Demonstrates Oncostatic Activity in the Therapeutic and Preventive Model of Breast Carcinoma

Authors

KUBATKA, P. (guarantor), M. KELLO, K. KAJO, M. SAMEC, A. LISKOVA, K. JASEK, L. KOKLESOVA, T. KURUC, M. ADAMKOV, Karel ŠMEJKAL (203 Czech Republic, belonging to the institution), Emil ŠVAJDLENKA (203 Czech Republic, belonging to the institution), P. SOLAR, M. PEC, D. BUSSELBERG, V. SADLONOVA and J. MOJZIS

Edition

International Journal of Molecular Sciences, Basel, Multidisciplinary Digital Publishing Institute, 2021, 1422-0067

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30104 Pharmacology and pharmacy

Country of publisher

Switzerland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 6.208

RIV identification code

RIV/00216224:14160/21:00123949

Organization unit

Faculty of Pharmacy

DOI

http://dx.doi.org/10.3390/ijms22010183

UT WoS

000606151100001

Keywords in English

angiogenesis; apoptosis; breast cancer; cancer stem cells; cell proliferation; epigenetics; MCF-7 cells; MDA-MB-231 cells; mouse; rat; Rhus coriaria; sumac

Abstract

V originále

Comprehensive scientific data provide evidence that isolated phytochemicals or whole plant foods may beneficially modify carcinogenesis. The aim of this study was to evaluate the oncostatic activities of Rhus coriaria L. (sumac) using animal models (rat and mouse), and cell lines of breast carcinoma. R. coriaria (as a powder) was administered through the diet at two concentrations (low dose: 0.1% (w/w) and high dose: 1 % (w/w)) for the duration of the experiment in a syngeneic 4T1 mouse and chemically-induced rat mammary carcinoma models. After autopsy, histopathological and molecular analyses of tumor samples in rodents were performed. Moreover, in vitro analyses using MCF-7 and MDA-MB-231 cells were conducted. The dominant metabolites present in tested R. coriaria methanolic extract were glycosides of gallic acid (possible gallotannins). In the mouse model, R. coriaria at a higher dose (1%) significantly decreased tumor volume by 27% when compared to controls. In addition, treated tumors showed significant dose-dependent decrease in mitotic activity index by 36.5% and 51% in comparison with the control group. In the chemoprevention study using rats, R. coriaria at a higher dose significantly reduced the tumor incidence by 20% and in lower dose non-significantly reduced tumor frequency by 29% when compared to controls. Evaluations of the mechanism of oncostatic action using valid clinical markers demonstrated several positive alterations in rat tumor cells after the treatment with R. coriaria. In this regard, histopathological analysis of treated tumor specimens showed robust dose-dependent decrease in the ratio of high-/low-grade carcinomas by 66% and 73% compared to controls. In treated rat carcinomas, we found significant caspase-3, Bax, and Bax/Bcl-2 expression increases; on the other side, a significant down-regulation of Bcl-2, Ki67, CD24, ALDH1, and EpCam expressions and MDA levels. When compared to control specimens, evaluation of epigenetic alterations in rat tumor cells in vivo showed significant dose-dependent decrease in lysine methylation status of H3K4m3 and H3K9m3 and dose-dependent increase in lysine acetylation in H4K16ac levels (H4K20m3 was not changed) in treated groups. However, only in lower dose of sumac were significant decreases in the expression of oncogenic miR210 and increase of tumor-suppressive miR145 (miR21, miR22, and miR155 were not changed) observed. Finally, only in lower sumac dose, significant decreases in methylation status of three out of five gene promoters-ATM, PTEN, and TIMP3 (PITX2 and RASSF1 promoters were not changed). In vitro evaluations using methanolic extract of R. coriaria showed significant anticancer efficacy in MCF-7 and MDA-MB-231 cells (using Resazurin, cell cycle, annexin V/PI, caspase-3/7, Bcl-2, PARP, and mitochondrial membrane potential analyses). In conclusion, sumac demonstrated significant oncostatic activities in rodent models of breast carcinoma that were validated by mechanistic studies in vivo and in vitro.

Citovat

KUBATKA, P., M. KELLO, K. KAJO, M. SAMEC, A. LISKOVA, K. JASEK, L. KOKLESOVA, T. KURUC, M. ADAMKOV, Karel ŠMEJKAL, Emil ŠVAJDLENKA, P. SOLAR, M. PEC, D. BUSSELBERG, V. SADLONOVA and J. MOJZIS. Rhus coriaria L. (Sumac) Demonstrates Oncostatic Activity in the Therapeutic and Preventive Model of Breast Carcinoma. International Journal of Molecular Sciences. Basel: Multidisciplinary Digital Publishing Institute, 2021, vol. 22, No 1, p. 1-30. ISSN 1422-0067. Available from: https://dx.doi.org/10.3390/ijms22010183.

@article{1826756,
   author = {Kubatka, P. and Kello, M. and Kajo, K. and Samec, M. and Liskova, A. and Jasek, K. and Koklesova, L. and Kuruc, T. and Adamkov, M. and Šmejkal, Karel and Švajdlenka, Emil and Solar, P. and Pec, M. and Busselberg, D. and Sadlonova, V. and Mojzis, J.},
   article_location = {Basel},
   article_number = {1},
   doi = {http://dx.doi.org/10.3390/ijms22010183},
   keywords = {angiogenesis; apoptosis; breast cancer; cancer stem cells; cell proliferation; epigenetics; MCF-7 cells; MDA-MB-231 cells; mouse; rat; Rhus coriaria; sumac},
   language = {eng},
   issn = {1422-0067},
   journal = {International Journal of Molecular Sciences},
   title = {Rhus coriaria L. (Sumac) Demonstrates Oncostatic Activity in the Therapeutic and Preventive Model of Breast Carcinoma},
   url = {https://www.mdpi.com/1422-0067/22/1/183},
   volume = {22},
   year = {2021}
}

TY  - JOUR
ID  - 1826756
AU  - Kubatka, P. - Kello, M. - Kajo, K. - Samec, M. - Liskova, A. - Jasek, K. - Koklesova, L. - Kuruc, T. - Adamkov, M. - Šmejkal, Karel - Švajdlenka, Emil - Solar, P. - Pec, M. - Busselberg, D. - Sadlonova, V. - Mojzis, J.
PY  - 2021
TI  - Rhus coriaria L. (Sumac) Demonstrates Oncostatic Activity in the Therapeutic and Preventive Model of Breast Carcinoma
JF  - International Journal of Molecular Sciences
VL  - 22
IS  - 1
SP  - 1-30
EP  - 1-30
PB  - Multidisciplinary Digital Publishing Institute
SN  - 14220067
KW  - angiogenesis
KW  - apoptosis
KW  - breast cancer
KW  - cancer stem cells
KW  - cell proliferation
KW  - epigenetics
KW  - MCF-7 cells
KW  - MDA-MB-231 cells
KW  - mouse
KW  - rat
KW  - Rhus coriaria
KW  - sumac
UR  - https://www.mdpi.com/1422-0067/22/1/183
N2  - Comprehensive scientific data provide evidence that isolated phytochemicals or whole plant foods may beneficially modify carcinogenesis. The aim of this study was to evaluate the oncostatic activities of Rhus coriaria L. (sumac) using animal models (rat and mouse), and cell lines of breast carcinoma. R. coriaria (as a powder) was administered through the diet at two concentrations (low dose: 0.1% (w/w) and high dose: 1 % (w/w)) for the duration of the experiment in a syngeneic 4T1 mouse and chemically-induced rat mammary carcinoma models. After autopsy, histopathological and molecular analyses of tumor samples in rodents were performed. Moreover, in vitro analyses using MCF-7 and MDA-MB-231 cells were conducted. The dominant metabolites present in tested R. coriaria methanolic extract were glycosides of gallic acid (possible gallotannins). In the mouse model, R. coriaria at a higher dose (1%) significantly decreased tumor volume by 27% when compared to controls. In addition, treated tumors showed significant dose-dependent decrease in mitotic activity index by 36.5% and 51% in comparison with the control group. In the chemoprevention study using rats, R. coriaria at a higher dose significantly reduced the tumor incidence by 20% and in lower dose non-significantly reduced tumor frequency by 29% when compared to controls. Evaluations of the mechanism of oncostatic action using valid clinical markers demonstrated several positive alterations in rat tumor cells after the treatment with R. coriaria. In this regard, histopathological analysis of treated tumor specimens showed robust dose-dependent decrease in the ratio of high-/low-grade carcinomas by 66% and 73% compared to controls. In treated rat carcinomas, we found significant caspase-3, Bax, and Bax/Bcl-2 expression increases; on the other side, a significant down-regulation of Bcl-2, Ki67, CD24, ALDH1, and EpCam expressions and MDA levels. When compared to control specimens, evaluation of epigenetic alterations in rat tumor cells in vivo showed significant dose-dependent decrease in lysine methylation status of H3K4m3 and H3K9m3 and dose-dependent increase in lysine acetylation in H4K16ac levels (H4K20m3 was not changed) in treated groups. However, only in lower dose of sumac were significant decreases in the expression of oncogenic miR210 and increase of tumor-suppressive miR145 (miR21, miR22, and miR155 were not changed) observed. Finally, only in lower sumac dose, significant decreases in methylation status of three out of five gene promoters-ATM, PTEN, and TIMP3 (PITX2 and RASSF1 promoters were not changed). In vitro evaluations using methanolic extract of R. coriaria showed significant anticancer efficacy in MCF-7 and MDA-MB-231 cells (using Resazurin, cell cycle, annexin V/PI, caspase-3/7, Bcl-2, PARP, and mitochondrial membrane potential analyses). In conclusion, sumac demonstrated significant oncostatic activities in rodent models of breast carcinoma that were validated by mechanistic studies in vivo and in vitro.
ER  -

KUBATKA, P., M. KELLO, K. KAJO, M. SAMEC, A. LISKOVA, K. JASEK, L. KOKLESOVA, T. KURUC, M. ADAMKOV, Karel ŠMEJKAL, Emil ŠVAJDLENKA, P. SOLAR, M. PEC, D. BUSSELBERG, V. SADLONOVA and J. MOJZIS. Rhus coriaria L. (Sumac) Demonstrates Oncostatic Activity in the Therapeutic and Preventive Model of Breast Carcinoma. \textit{International Journal of Molecular Sciences}. Basel: Multidisciplinary Digital Publishing Institute, 2021, vol.~22, No~1, p.~1-30. ISSN~1422-0067. Available from: https://dx.doi.org/10.3390/ijms22010183.

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