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Antitumor Effects of Natural Bioactive Ursolic Acid in Embryonic Cancer Stem Cells

Embryonic cancer cells (CSCs) could cause different types of cancer, a skill that makes them even more dangerous than other cancer cells. Identifying CSCs using natural products is a good option as it inhibits the recurrence of cancer with moderate various effects. Ursolic acid (UA) is a pentacyclic...

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Autores principales: Kang, Dong Young, Sp, Nipin, Jang, Kyoung-Jin, Jo, Eun Seong, Bae, Se Won, Yang, Young Mok
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8866021/
https://www.ncbi.nlm.nih.gov/pubmed/35222644
http://dx.doi.org/10.1155/2022/6737248
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author Kang, Dong Young
Sp, Nipin
Jang, Kyoung-Jin
Jo, Eun Seong
Bae, Se Won
Yang, Young Mok
author_facet Kang, Dong Young
Sp, Nipin
Jang, Kyoung-Jin
Jo, Eun Seong
Bae, Se Won
Yang, Young Mok
author_sort Kang, Dong Young
collection PubMed
description Embryonic cancer cells (CSCs) could cause different types of cancer, a skill that makes them even more dangerous than other cancer cells. Identifying CSCs using natural products is a good option as it inhibits the recurrence of cancer with moderate various effects. Ursolic acid (UA) is a pentacyclic triterpenoid extracted from fruit and herbal remedies and has known anticancer functions against various cancer cells. However, its potential against CSCs remains uncertain. This study was planned to examine the induction of cell apoptosis by the UA. For cell signaling studies, we performed experiments, which are real-time qPCR and immunoblotting. Also, various cellular processes were analyzed using flow cytometry. The results raised a barrier to cell proliferation by the UA in NTERA-2 and NCCIT cells. Morphological studies also confirmed the UA's ability to cause cell death in embryonic CSCs. Examination of cell death importation showed that the UA formed the expression of the iNOS and thus the cell generation and mitochondrial reactive oxygen generation, which created a reaction to cellular DNA damage by raising the protein levels of phospho-histone ATR and ATM. In addition, the UA created the binding of the G0/G1 cell cycle to NTERA-2 and NCCIT cells, improved the expression levels of p21 and p27, and reduced the expression levels of CDK4, cyclin D1, and cyclin E, confirming the UA's ability to initiate cell cycle arrest. Finally, the UA created an internal mechanism of apoptosis in the embryonic CSC using BAX and cytochrome c regulation as well as the regulation of BCL-xL and BCL-2 proteins. Therefore, UA could be the best candidate for targeting CSCs and thus suppressing the emergence of cancer.
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spelling pubmed-88660212022-02-24 Antitumor Effects of Natural Bioactive Ursolic Acid in Embryonic Cancer Stem Cells Kang, Dong Young Sp, Nipin Jang, Kyoung-Jin Jo, Eun Seong Bae, Se Won Yang, Young Mok J Oncol Research Article Embryonic cancer cells (CSCs) could cause different types of cancer, a skill that makes them even more dangerous than other cancer cells. Identifying CSCs using natural products is a good option as it inhibits the recurrence of cancer with moderate various effects. Ursolic acid (UA) is a pentacyclic triterpenoid extracted from fruit and herbal remedies and has known anticancer functions against various cancer cells. However, its potential against CSCs remains uncertain. This study was planned to examine the induction of cell apoptosis by the UA. For cell signaling studies, we performed experiments, which are real-time qPCR and immunoblotting. Also, various cellular processes were analyzed using flow cytometry. The results raised a barrier to cell proliferation by the UA in NTERA-2 and NCCIT cells. Morphological studies also confirmed the UA's ability to cause cell death in embryonic CSCs. Examination of cell death importation showed that the UA formed the expression of the iNOS and thus the cell generation and mitochondrial reactive oxygen generation, which created a reaction to cellular DNA damage by raising the protein levels of phospho-histone ATR and ATM. In addition, the UA created the binding of the G0/G1 cell cycle to NTERA-2 and NCCIT cells, improved the expression levels of p21 and p27, and reduced the expression levels of CDK4, cyclin D1, and cyclin E, confirming the UA's ability to initiate cell cycle arrest. Finally, the UA created an internal mechanism of apoptosis in the embryonic CSC using BAX and cytochrome c regulation as well as the regulation of BCL-xL and BCL-2 proteins. Therefore, UA could be the best candidate for targeting CSCs and thus suppressing the emergence of cancer. Hindawi 2022-02-16 /pmc/articles/PMC8866021/ /pubmed/35222644 http://dx.doi.org/10.1155/2022/6737248 Text en Copyright © 2022 Dong Young Kang et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Kang, Dong Young
Sp, Nipin
Jang, Kyoung-Jin
Jo, Eun Seong
Bae, Se Won
Yang, Young Mok
Antitumor Effects of Natural Bioactive Ursolic Acid in Embryonic Cancer Stem Cells
title Antitumor Effects of Natural Bioactive Ursolic Acid in Embryonic Cancer Stem Cells
title_full Antitumor Effects of Natural Bioactive Ursolic Acid in Embryonic Cancer Stem Cells
title_fullStr Antitumor Effects of Natural Bioactive Ursolic Acid in Embryonic Cancer Stem Cells
title_full_unstemmed Antitumor Effects of Natural Bioactive Ursolic Acid in Embryonic Cancer Stem Cells
title_short Antitumor Effects of Natural Bioactive Ursolic Acid in Embryonic Cancer Stem Cells
title_sort antitumor effects of natural bioactive ursolic acid in embryonic cancer stem cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8866021/
https://www.ncbi.nlm.nih.gov/pubmed/35222644
http://dx.doi.org/10.1155/2022/6737248
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