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Betulinic Acid Modulates the Expression of HSPA and Activates Apoptosis in Two Cell Lines of Human Colorectal Cancer

Betulinic acid (BA) is a pentacyclic triterpene usually isolated from botanical sources. Numerous studies have reported the inhibitory effect of BA against human colorectal cancer cells (CRC). However, its effect on the expression of the molecular chaperone HSPA is unclear. The aim of this research...

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Autores principales: Yurasakpong, Laphatrada, Nantasenamat, Chanin, Nobsathian, Saksit, Chaithirayanon, Kulathida, Apisawetakan, Somjai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8588033/
https://www.ncbi.nlm.nih.gov/pubmed/34770786
http://dx.doi.org/10.3390/molecules26216377
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author Yurasakpong, Laphatrada
Nantasenamat, Chanin
Nobsathian, Saksit
Chaithirayanon, Kulathida
Apisawetakan, Somjai
author_facet Yurasakpong, Laphatrada
Nantasenamat, Chanin
Nobsathian, Saksit
Chaithirayanon, Kulathida
Apisawetakan, Somjai
author_sort Yurasakpong, Laphatrada
collection PubMed
description Betulinic acid (BA) is a pentacyclic triterpene usually isolated from botanical sources. Numerous studies have reported the inhibitory effect of BA against human colorectal cancer cells (CRC). However, its effect on the expression of the molecular chaperone HSPA is unclear. The aim of this research is to investigate the anti-cancer activities of BA purified from Piper retrofractum and study its effect on the expression of HSPA in colorectal cancer HCT116 and SW480 cells. The viability of both cancer cells was reduced after they were treated with an increasing dosage of BA. Flow cytometry assay revealed that levels of cell apoptosis significantly increased after incubation with BA in both cancer cells. Pro-apoptotic markers including Bax, cleaved-caspase-3 and cleaved-caspase-9 were increased while anti-apoptotic marker Bcl-2 was decreased after BA treatment. Western blot also showed that the expression of HSPA fluctuated upon BA treatment, whereby HSPA was increased at lower BA concentrations while at higher BA concentrations HSPA expression was decreased. Preliminary molecular docking assay showed that BA can bind to the nucleotide binding domain of the HSP70 at its ADP-bound state of the HSP70. Although further research is needed to comprehend the BA-HSPA interaction, our findings indicate that BA can be considered as potential candidate for the development of new treatment for colorectal cancer.
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spelling pubmed-85880332021-11-13 Betulinic Acid Modulates the Expression of HSPA and Activates Apoptosis in Two Cell Lines of Human Colorectal Cancer Yurasakpong, Laphatrada Nantasenamat, Chanin Nobsathian, Saksit Chaithirayanon, Kulathida Apisawetakan, Somjai Molecules Article Betulinic acid (BA) is a pentacyclic triterpene usually isolated from botanical sources. Numerous studies have reported the inhibitory effect of BA against human colorectal cancer cells (CRC). However, its effect on the expression of the molecular chaperone HSPA is unclear. The aim of this research is to investigate the anti-cancer activities of BA purified from Piper retrofractum and study its effect on the expression of HSPA in colorectal cancer HCT116 and SW480 cells. The viability of both cancer cells was reduced after they were treated with an increasing dosage of BA. Flow cytometry assay revealed that levels of cell apoptosis significantly increased after incubation with BA in both cancer cells. Pro-apoptotic markers including Bax, cleaved-caspase-3 and cleaved-caspase-9 were increased while anti-apoptotic marker Bcl-2 was decreased after BA treatment. Western blot also showed that the expression of HSPA fluctuated upon BA treatment, whereby HSPA was increased at lower BA concentrations while at higher BA concentrations HSPA expression was decreased. Preliminary molecular docking assay showed that BA can bind to the nucleotide binding domain of the HSP70 at its ADP-bound state of the HSP70. Although further research is needed to comprehend the BA-HSPA interaction, our findings indicate that BA can be considered as potential candidate for the development of new treatment for colorectal cancer. MDPI 2021-10-22 /pmc/articles/PMC8588033/ /pubmed/34770786 http://dx.doi.org/10.3390/molecules26216377 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Yurasakpong, Laphatrada
Nantasenamat, Chanin
Nobsathian, Saksit
Chaithirayanon, Kulathida
Apisawetakan, Somjai
Betulinic Acid Modulates the Expression of HSPA and Activates Apoptosis in Two Cell Lines of Human Colorectal Cancer
title Betulinic Acid Modulates the Expression of HSPA and Activates Apoptosis in Two Cell Lines of Human Colorectal Cancer
title_full Betulinic Acid Modulates the Expression of HSPA and Activates Apoptosis in Two Cell Lines of Human Colorectal Cancer
title_fullStr Betulinic Acid Modulates the Expression of HSPA and Activates Apoptosis in Two Cell Lines of Human Colorectal Cancer
title_full_unstemmed Betulinic Acid Modulates the Expression of HSPA and Activates Apoptosis in Two Cell Lines of Human Colorectal Cancer
title_short Betulinic Acid Modulates the Expression of HSPA and Activates Apoptosis in Two Cell Lines of Human Colorectal Cancer
title_sort betulinic acid modulates the expression of hspa and activates apoptosis in two cell lines of human colorectal cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8588033/
https://www.ncbi.nlm.nih.gov/pubmed/34770786
http://dx.doi.org/10.3390/molecules26216377
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