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Flavokawain A Reduces Tumor-Initiating Properties and Stemness of Prostate Cancer

We have previously demonstrated the in vivo chemopreventive efficacy of flavokawain A (FKA), a novel chalcone from the kava plant, in prostate carcinogenesis models. However, the mechanisms of the anticarcinogenic effects of FKA remain largely unknown. We evaluated the effect of FKA on prostate tumo...

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Autores principales: Song, Liankun, Mino, Merci, Yamak, Jana, Nguyen, Vyvyan, Lopez, Derron, Pham, Victor, Fazelpour, Ali, Le, Vinh, Fu, Dongjun, Tippin, Matthew, Uchio, Edward, Zi, Xiaolin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9326116/
https://www.ncbi.nlm.nih.gov/pubmed/35912174
http://dx.doi.org/10.3389/fonc.2022.943846
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author Song, Liankun
Mino, Merci
Yamak, Jana
Nguyen, Vyvyan
Lopez, Derron
Pham, Victor
Fazelpour, Ali
Le, Vinh
Fu, Dongjun
Tippin, Matthew
Uchio, Edward
Zi, Xiaolin
author_facet Song, Liankun
Mino, Merci
Yamak, Jana
Nguyen, Vyvyan
Lopez, Derron
Pham, Victor
Fazelpour, Ali
Le, Vinh
Fu, Dongjun
Tippin, Matthew
Uchio, Edward
Zi, Xiaolin
author_sort Song, Liankun
collection PubMed
description We have previously demonstrated the in vivo chemopreventive efficacy of flavokawain A (FKA), a novel chalcone from the kava plant, in prostate carcinogenesis models. However, the mechanisms of the anticarcinogenic effects of FKA remain largely unknown. We evaluated the effect of FKA on prostate tumor spheroid formation by prostate cancer stem cells, which were sorted out from CD44+/CD133+ prostate cancer cells 22Rv1 and DU145. FKA treatment significantly decreased both the size and numbers of the tumor spheroids over different generations of spheroid passages. In addition, the dietary feeding of FKA-formulated food to Nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice bearing CD44+/CD133+ 22Rv1 xenograft tumors resulted in a significant reduction of tumor growth compared to those fed with vehicle control food–fed mice. Furthermore, the expression of stem cell markers, such as Nanog, Oct4, and CD44, were markedly downregulated in both tumor spheroids and tumor tissues. We also observed that FKA inhibits Ubc12 neddylation, c-Myc, and keratin-8 expression in both CD44+/CD133+ prostate tumor spheroids and xenograft tumors. Our results suggest that FKA can reduce the tumor-initiating properties and stemness of prostate cancer, which provides a new mechanism for the chemoprevention efficacy of FKA.
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spelling pubmed-93261162022-07-28 Flavokawain A Reduces Tumor-Initiating Properties and Stemness of Prostate Cancer Song, Liankun Mino, Merci Yamak, Jana Nguyen, Vyvyan Lopez, Derron Pham, Victor Fazelpour, Ali Le, Vinh Fu, Dongjun Tippin, Matthew Uchio, Edward Zi, Xiaolin Front Oncol Oncology We have previously demonstrated the in vivo chemopreventive efficacy of flavokawain A (FKA), a novel chalcone from the kava plant, in prostate carcinogenesis models. However, the mechanisms of the anticarcinogenic effects of FKA remain largely unknown. We evaluated the effect of FKA on prostate tumor spheroid formation by prostate cancer stem cells, which were sorted out from CD44+/CD133+ prostate cancer cells 22Rv1 and DU145. FKA treatment significantly decreased both the size and numbers of the tumor spheroids over different generations of spheroid passages. In addition, the dietary feeding of FKA-formulated food to Nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice bearing CD44+/CD133+ 22Rv1 xenograft tumors resulted in a significant reduction of tumor growth compared to those fed with vehicle control food–fed mice. Furthermore, the expression of stem cell markers, such as Nanog, Oct4, and CD44, were markedly downregulated in both tumor spheroids and tumor tissues. We also observed that FKA inhibits Ubc12 neddylation, c-Myc, and keratin-8 expression in both CD44+/CD133+ prostate tumor spheroids and xenograft tumors. Our results suggest that FKA can reduce the tumor-initiating properties and stemness of prostate cancer, which provides a new mechanism for the chemoprevention efficacy of FKA. Frontiers Media S.A. 2022-07-13 /pmc/articles/PMC9326116/ /pubmed/35912174 http://dx.doi.org/10.3389/fonc.2022.943846 Text en Copyright © 2022 Song, Mino, Yamak, Nguyen, Lopez, Pham, Fazelpour, Le, Fu, Tippin, Uchio and Zi 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 Oncology
Song, Liankun
Mino, Merci
Yamak, Jana
Nguyen, Vyvyan
Lopez, Derron
Pham, Victor
Fazelpour, Ali
Le, Vinh
Fu, Dongjun
Tippin, Matthew
Uchio, Edward
Zi, Xiaolin
Flavokawain A Reduces Tumor-Initiating Properties and Stemness of Prostate Cancer
title Flavokawain A Reduces Tumor-Initiating Properties and Stemness of Prostate Cancer
title_full Flavokawain A Reduces Tumor-Initiating Properties and Stemness of Prostate Cancer
title_fullStr Flavokawain A Reduces Tumor-Initiating Properties and Stemness of Prostate Cancer
title_full_unstemmed Flavokawain A Reduces Tumor-Initiating Properties and Stemness of Prostate Cancer
title_short Flavokawain A Reduces Tumor-Initiating Properties and Stemness of Prostate Cancer
title_sort flavokawain a reduces tumor-initiating properties and stemness of prostate cancer
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9326116/
https://www.ncbi.nlm.nih.gov/pubmed/35912174
http://dx.doi.org/10.3389/fonc.2022.943846
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