Aronia melanocarpa L. fruit peels show anti-cancer effects in
preclinical models of breast carcinoma: The perspectives in the
chemoprevention and therapy modulation

J 2024

Aronia melanocarpa L. fruit peels show anti-cancer effects in preclinical models of breast carcinoma: The perspectives in the chemoprevention and therapy modulation

DVORSKA, Dana; Alena MAZURAKOVA; Lenka LACKOVA; Dominika SEBOVA; Karol KAJO et. al.

Basic information

Original name

Aronia melanocarpa L. fruit peels show anti-cancer effects in preclinical models of breast carcinoma: The perspectives in the chemoprevention and therapy modulation

Authors

DVORSKA, Dana (703 Slovakia); Alena MAZURAKOVA (703 Slovakia); Lenka LACKOVA (703 Slovakia); Dominika SEBOVA (703 Slovakia); Karol KAJO (703 Slovakia); Marek SAMEC (703 Slovakia); Dusan BRANY (703 Slovakia); Emil ŠVAJDLENKA (203 Czech Republic, belonging to the institution); Jakub TREML (203 Czech Republic, belonging to the institution); Sandra MERSAKOVA (703 Slovakia); Jan STRNADEL (703 Slovakia); Marian ADAMKOV (703 Slovakia); Zora LASABOVA (703 Slovakia); Kamil BIRINGER (703 Slovakia); Jan MOJZIS (703 Slovakia); Dietrich BUSSELBERG (634 Qatar); Karel ŠMEJKAL (203 Czech Republic, belonging to the institution); Martin KELLO (703 Slovakia) and Peter KUBATKA (703 Slovakia)

Edition

Frontiers in Oncology, Lausanne, FRONTIERS MEDIA SA, 2024, 2234-943X

Other information

Language

English

Type of outcome

Article in a journal

Field of Study

30204 Oncology

Country of publisher

Switzerland

Confidentiality degree

is not subject to a state or trade secret

References:

URL

Impact factor

Impact factor: 3.500 in 2023

RIV identification code

RIV/00216224:14160/24:00139007

Organization unit

Faculty of Pharmacy

DOI

http://dx.doi.org/10.3389/fonc.2024.1463656

UT WoS

001339459500001

EID Scopus

2-s2.0-85207005369

Keywords in English

Aronia melanocarpa L.; rodent models; breast carcinoma; in vitro models; mechanism of action; epigenetics

Abstract

V originále

Introduction Within oncology research, there is a high effort for new approaches to prevent and treat cancer as a life-threatening disease. Specific plant species that adapt to harsh conditions may possess unique properties that may be utilized in the management of cancer. Hypothesis Chokeberry fruit is rich in secondary metabolites with anti-cancer activities potentially useful in cancer prevention and treatment. Aims of the study and Methods Based on mentioned hypothesis, the main goal of our study was to evaluate the antitumor effects of dietary administered Aronia melanocarpa L. fruit peels (in two concentrations of 0.3 and 3% [w/w]) in the therapeutic syngeneic 4T1 mouse adenocarcinoma model, the chemopreventive model of chemically induced mammary carcinogenesis in rats, a cell antioxidant assay, and robust in vitro analyses using MCF-7 and MDA-MB-231 cancer cells. Results The dominant metabolites in the A. melanocarpa fruit peel extract tested were phenolic derivatives classified as anthocyanins and procyanidins. In a therapeutic model, aronia significantly reduced the volume of 4T1 tumors at both higher and lower doses. In the same tumors, we noted a significant dose-dependent decrease in the mitotic activity index compared to the control. In the chemopreventive model, the expression of Bax was significantly increased by aronia at both doses. Additionally, aronia decreased Bcl-2 and VEGF levels, increasing the Bax/Bcl-2 ratio compared to the control group. The cytoplasmic expression of caspase-3 was significantly enhanced when aronia was administered at a higher dosage, in contrast to both the control group and the aronia group treated with a lower dosage. Furthermore, the higher dosage of aronia exhibited a significant reduction in the expression of the tumor stem cell marker CD133 compared to the control group. In addition, the examination of aronia`s epigenetic impact on tumor tissue through in vivo analyses revealed significant alterations in histone chemical modifications, specifically H3K4m3 and H3K9m3, miRNAs expression (miR155, miR210, and miR34a) and methylation status of tumor suppressor genes (PTEN and TIMP3). In vitro studies utilizing a methanolic extract of A.melanocarpa demonstrated significant anti-cancer properties in the MCF-7 and MDA-MB-231 cell lines. Various analyses, including Resazurin, cell cycle, annexin V/PI, caspase-3/7, Bcl-2, PARP, and mitochondrial membrane potential, were conducted in this regard. Additionally, the aronia extract enhanced the responsiveness to epirubicin in both cancer cell lines. Conclusion This study is the first to analyze the antitumor effect of A. melanocarpa in selected models of experimental breast carcinoma in vivo and in vitro. The utilization of the antitumor effects of aronia in clinical practice is still minimal and requires precise and long-term clinical evaluations. Individualized cancer-type profiling and patient stratification are crucial for effectively implementing plant nutraceuticals within targeted anti-cancer strategies in clinical oncology.

Cite

DVORSKA, Dana; Alena MAZURAKOVA; Lenka LACKOVA; Dominika SEBOVA; Karol KAJO; Marek SAMEC; Dusan BRANY; Emil ŠVAJDLENKA; Jakub TREML; Sandra MERSAKOVA; Jan STRNADEL; Marian ADAMKOV; Zora LASABOVA; Kamil BIRINGER; Jan MOJZIS; Dietrich BUSSELBERG; Karel ŠMEJKAL; Martin KELLO and Peter KUBATKA. Aronia melanocarpa L. fruit peels show anti-cancer effects in preclinical models of breast carcinoma: The perspectives in the chemoprevention and therapy modulation. Frontiers in Oncology. Lausanne: FRONTIERS MEDIA SA, 2024, vol. 14, Neuvedeno, p. 1-25. ISSN 2234-943X. Available from: https://dx.doi.org/10.3389/fonc.2024.1463656.

@article{2481977,
   author = {Dvorska, Dana and Mazurakova, Alena and Lackova, Lenka and Sebova, Dominika and Kajo, Karol and Samec, Marek and Brany, Dusan and Švajdlenka, Emil and Treml, Jakub and Mersakova, Sandra and Strnadel, Jan and Adamkov, Marian and Lasabova, Zora and Biringer, Kamil and Mojzis, Jan and Busselberg, Dietrich and Šmejkal, Karel and Kello, Martin and Kubatka, Peter},
   article_location = {Lausanne},
   article_number = {Neuvedeno},
   doi = {http://dx.doi.org/10.3389/fonc.2024.1463656},
   keywords = {Aronia melanocarpa L.; rodent models; breast carcinoma; in vitro models; mechanism of action; epigenetics},
   language = {eng},
   issn = {2234-943X},
   journal = {Frontiers in Oncology},
   title = {Aronia melanocarpa L. fruit peels show anti-cancer effects in preclinical models of breast carcinoma: The perspectives in the chemoprevention and therapy modulation},
   url = {https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2024.1463656/full},
   volume = {14},
   year = {2024}
}

TY  - JOUR
ID  - 2481977
AU  - Dvorska, Dana - Mazurakova, Alena - Lackova, Lenka - Sebova, Dominika - Kajo, Karol - Samec, Marek - Brany, Dusan - Švajdlenka, Emil - Treml, Jakub - Mersakova, Sandra - Strnadel, Jan - Adamkov, Marian - Lasabova, Zora - Biringer, Kamil - Mojzis, Jan - Busselberg, Dietrich - Šmejkal, Karel - Kello, Martin - Kubatka, Peter
PY  - 2024
TI  - Aronia melanocarpa L. fruit peels show anti-cancer effects in preclinical models of breast carcinoma: The perspectives in the chemoprevention and therapy modulation
JF  - Frontiers in Oncology
VL  - 14
IS  - Neuvedeno
SP  - 1-25
EP  - 1-25
PB  - FRONTIERS MEDIA SA
SN  - 2234943X
KW  - Aronia melanocarpa L.
KW  - rodent models
KW  - breast carcinoma
KW  - in vitro models
KW  - mechanism of action
KW  - epigenetics
UR  - https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2024.1463656/full
N2  - Introduction Within oncology research, there is a high effort for new approaches to prevent and treat cancer as a life-threatening disease. Specific plant species that adapt to harsh conditions may possess unique properties that may be utilized in the management of cancer. Hypothesis Chokeberry fruit is rich in secondary metabolites with anti-cancer activities potentially useful in cancer prevention and treatment. Aims of the study and Methods Based on mentioned hypothesis, the main goal of our study was to evaluate the antitumor effects of dietary administered Aronia melanocarpa L. fruit peels (in two concentrations of 0.3 and 3% [w/w]) in the therapeutic syngeneic 4T1 mouse adenocarcinoma model, the chemopreventive model of chemically induced mammary carcinogenesis in rats, a cell antioxidant assay, and robust in vitro analyses using MCF-7 and MDA-MB-231 cancer cells. Results The dominant metabolites in the A. melanocarpa fruit peel extract tested were phenolic derivatives classified as anthocyanins and procyanidins. In a therapeutic model, aronia significantly reduced the volume of 4T1 tumors at both higher and lower doses. In the same tumors, we noted a significant dose-dependent decrease in the mitotic activity index compared to the control. In the chemopreventive model, the expression of Bax was significantly increased by aronia at both doses. Additionally, aronia decreased Bcl-2 and VEGF levels, increasing the Bax/Bcl-2 ratio compared to the control group. The cytoplasmic expression of caspase-3 was significantly enhanced when aronia was administered at a higher dosage, in contrast to both the control group and the aronia group treated with a lower dosage. Furthermore, the higher dosage of aronia exhibited a significant reduction in the expression of the tumor stem cell marker CD133 compared to the control group. In addition, the examination of aronia`s epigenetic impact on tumor tissue through in vivo analyses revealed significant alterations in histone chemical modifications, specifically H3K4m3 and H3K9m3, miRNAs expression (miR155, miR210, and miR34a) and methylation status of tumor suppressor genes (PTEN and TIMP3). In vitro studies utilizing a methanolic extract of A.melanocarpa demonstrated significant anti-cancer properties in the MCF-7 and MDA-MB-231 cell lines. Various analyses, including Resazurin, cell cycle, annexin V/PI, caspase-3/7, Bcl-2, PARP, and mitochondrial membrane potential, were conducted in this regard. Additionally, the aronia extract enhanced the responsiveness to epirubicin in both cancer cell lines. Conclusion This study is the first to analyze the antitumor effect of A. melanocarpa in selected models of experimental breast carcinoma in vivo and in vitro. The utilization of the antitumor effects of aronia in clinical practice is still minimal and requires precise and long-term clinical evaluations. Individualized cancer-type profiling and patient stratification are crucial for effectively implementing plant nutraceuticals within targeted anti-cancer strategies in clinical oncology.
ER  -

DVORSKA, Dana; Alena MAZURAKOVA; Lenka LACKOVA; Dominika SEBOVA; Karol KAJO; Marek SAMEC; Dusan BRANY; Emil ŠVAJDLENKA; Jakub TREML; Sandra MERSAKOVA; Jan STRNADEL; Marian ADAMKOV; Zora LASABOVA; Kamil BIRINGER; Jan MOJZIS; Dietrich BUSSELBERG; Karel ŠMEJKAL; Martin KELLO and Peter KUBATKA. Aronia melanocarpa L. fruit peels show anti-cancer effects in preclinical models of breast carcinoma: The perspectives in the chemoprevention and therapy modulation. \textit{Frontiers in Oncology}. Lausanne: FRONTIERS MEDIA SA, 2024, vol.~14, Neuvedeno, p.~1-25. ISSN~2234-943X. Available from: https://dx.doi.org/10.3389/fonc.2024.1463656.

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