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Anti-cancer activity of Chaga mushroom (Inonotus obliquus) against dog bladder cancer organoids

Despite its disadvantages, chemotherapy is still commonly used for the treatment of bladder cancer (BC). Developing natural supplements that can target cancer stem cells (CSCs) which cause drug resistance and distant metastasis is necessary. Chaga mushrooms are popular to have several health-promoti...

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Autores principales: Abugomaa, Amira, Elbadawy, Mohamed, Ishihara, Yusuke, Yamamoto, Haru, Kaneda, Masahiro, Yamawaki, Hideyuki, Shinohara, Yuta, Usui, Tatsuya, Sasaki, Kazuaki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10154587/
https://www.ncbi.nlm.nih.gov/pubmed/37153767
http://dx.doi.org/10.3389/fphar.2023.1159516
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author Abugomaa, Amira
Elbadawy, Mohamed
Ishihara, Yusuke
Yamamoto, Haru
Kaneda, Masahiro
Yamawaki, Hideyuki
Shinohara, Yuta
Usui, Tatsuya
Sasaki, Kazuaki
author_facet Abugomaa, Amira
Elbadawy, Mohamed
Ishihara, Yusuke
Yamamoto, Haru
Kaneda, Masahiro
Yamawaki, Hideyuki
Shinohara, Yuta
Usui, Tatsuya
Sasaki, Kazuaki
author_sort Abugomaa, Amira
collection PubMed
description Despite its disadvantages, chemotherapy is still commonly used for the treatment of bladder cancer (BC). Developing natural supplements that can target cancer stem cells (CSCs) which cause drug resistance and distant metastasis is necessary. Chaga mushrooms are popular to have several health-promoting and anti-cancer potentials. Organoid culture can recapitulate tumor heterogeneity, epithelial environment, and genetic and molecular imprints of the original tissues. In the previous study, we generated dog bladder cancer organoids (DBCO) as a novel experimental model of muscle-invasive BCO. Therefore, the present study aimed to examine the anti-tumor potentials of Chaga mushroom extract (Chaga) against DBCO. Four strains of DBCO were used in the present study. Treatment with Chaga inhibited the cell viability of DBCO in a concentration-dependent way. Treatment of DBCO with Chaga has significantly arrested its cell cycle and induced apoptosis. Expression of bladder CSC markers, CD44, C-MYC, SOX2, and YAP1, declined in the Chaga-treated DBCO. Also, Chaga inhibited the phosphorylation of ERK in DBCO. Expression of downstream signals of ERK, C-MYC, and Cyclins (Cyclin-A2, Cyclin-D1, Cyclin-E1, and CDK4) was also inhibited by Chaga in DBCO. Interestingly, the combinational treatment of DBCO with Chaga and anti-cancer drugs, vinblastine, mitoxantrone, or carboplatin, showed a potentiating activity. In vivo, Chaga administration decreased tumor growth and weight of DBCO-derived xenograft in mice with the induction of necrotic lesions. In conclusion, Chaga diminished the cell viability of DBCO by inhibiting proliferation-related signals and stemness conditions as well as by arresting the cell cycle. Collectively, these data suggest the value of Chaga as a promising natural supplement that could potentiate the effect of adjuvant chemotherapy, lower its adverse effects, and thus, limit the recurrence and metastasis of BC.
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spelling pubmed-101545872023-05-04 Anti-cancer activity of Chaga mushroom (Inonotus obliquus) against dog bladder cancer organoids Abugomaa, Amira Elbadawy, Mohamed Ishihara, Yusuke Yamamoto, Haru Kaneda, Masahiro Yamawaki, Hideyuki Shinohara, Yuta Usui, Tatsuya Sasaki, Kazuaki Front Pharmacol Pharmacology Despite its disadvantages, chemotherapy is still commonly used for the treatment of bladder cancer (BC). Developing natural supplements that can target cancer stem cells (CSCs) which cause drug resistance and distant metastasis is necessary. Chaga mushrooms are popular to have several health-promoting and anti-cancer potentials. Organoid culture can recapitulate tumor heterogeneity, epithelial environment, and genetic and molecular imprints of the original tissues. In the previous study, we generated dog bladder cancer organoids (DBCO) as a novel experimental model of muscle-invasive BCO. Therefore, the present study aimed to examine the anti-tumor potentials of Chaga mushroom extract (Chaga) against DBCO. Four strains of DBCO were used in the present study. Treatment with Chaga inhibited the cell viability of DBCO in a concentration-dependent way. Treatment of DBCO with Chaga has significantly arrested its cell cycle and induced apoptosis. Expression of bladder CSC markers, CD44, C-MYC, SOX2, and YAP1, declined in the Chaga-treated DBCO. Also, Chaga inhibited the phosphorylation of ERK in DBCO. Expression of downstream signals of ERK, C-MYC, and Cyclins (Cyclin-A2, Cyclin-D1, Cyclin-E1, and CDK4) was also inhibited by Chaga in DBCO. Interestingly, the combinational treatment of DBCO with Chaga and anti-cancer drugs, vinblastine, mitoxantrone, or carboplatin, showed a potentiating activity. In vivo, Chaga administration decreased tumor growth and weight of DBCO-derived xenograft in mice with the induction of necrotic lesions. In conclusion, Chaga diminished the cell viability of DBCO by inhibiting proliferation-related signals and stemness conditions as well as by arresting the cell cycle. Collectively, these data suggest the value of Chaga as a promising natural supplement that could potentiate the effect of adjuvant chemotherapy, lower its adverse effects, and thus, limit the recurrence and metastasis of BC. Frontiers Media S.A. 2023-04-19 /pmc/articles/PMC10154587/ /pubmed/37153767 http://dx.doi.org/10.3389/fphar.2023.1159516 Text en Copyright © 2023 Abugomaa, Elbadawy, Ishihara, Yamamoto, Kaneda, Yamawaki, Shinohara, Usui and Sasaki. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Abugomaa, Amira
Elbadawy, Mohamed
Ishihara, Yusuke
Yamamoto, Haru
Kaneda, Masahiro
Yamawaki, Hideyuki
Shinohara, Yuta
Usui, Tatsuya
Sasaki, Kazuaki
Anti-cancer activity of Chaga mushroom (Inonotus obliquus) against dog bladder cancer organoids
title Anti-cancer activity of Chaga mushroom (Inonotus obliquus) against dog bladder cancer organoids
title_full Anti-cancer activity of Chaga mushroom (Inonotus obliquus) against dog bladder cancer organoids
title_fullStr Anti-cancer activity of Chaga mushroom (Inonotus obliquus) against dog bladder cancer organoids
title_full_unstemmed Anti-cancer activity of Chaga mushroom (Inonotus obliquus) against dog bladder cancer organoids
title_short Anti-cancer activity of Chaga mushroom (Inonotus obliquus) against dog bladder cancer organoids
title_sort anti-cancer activity of chaga mushroom (inonotus obliquus) against dog bladder cancer organoids
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10154587/
https://www.ncbi.nlm.nih.gov/pubmed/37153767
http://dx.doi.org/10.3389/fphar.2023.1159516
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