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p53 Enhances Artemisia annua L. Polyphenols-Induced Cell Death Through Upregulation of p53-Dependent Targets and Cleavage of PARP1 and Lamin A/C in HCT116 Colorectal Cancer Cells

Plant-derived natural polyphenols exhibit anticancer activity without showing any noticeable toxicities to normal cells. The aim of this study was to investigate the role of p53 on the anticancer effect of polyphenols isolated from Korean Artemisia annua L. (pKAL) in HCT116 human colorectal cancer c...

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Autores principales: Jung, Eun Joo, Lee, Won Sup, Paramanantham, Anjugam, Kim, Hye Jung, Shin, Sung Chul, Kim, Gon Sup, Jung, Jin-Myung, Ryu, Chung Ho, Hong, Soon Chan, Chung, Ky Hyun, Kim, Choong Won
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7730414/
https://www.ncbi.nlm.nih.gov/pubmed/33297377
http://dx.doi.org/10.3390/ijms21239315
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author Jung, Eun Joo
Lee, Won Sup
Paramanantham, Anjugam
Kim, Hye Jung
Shin, Sung Chul
Kim, Gon Sup
Jung, Jin-Myung
Ryu, Chung Ho
Hong, Soon Chan
Chung, Ky Hyun
Kim, Choong Won
author_facet Jung, Eun Joo
Lee, Won Sup
Paramanantham, Anjugam
Kim, Hye Jung
Shin, Sung Chul
Kim, Gon Sup
Jung, Jin-Myung
Ryu, Chung Ho
Hong, Soon Chan
Chung, Ky Hyun
Kim, Choong Won
author_sort Jung, Eun Joo
collection PubMed
description Plant-derived natural polyphenols exhibit anticancer activity without showing any noticeable toxicities to normal cells. The aim of this study was to investigate the role of p53 on the anticancer effect of polyphenols isolated from Korean Artemisia annua L. (pKAL) in HCT116 human colorectal cancer cells. We confirmed that pKAL induced reactive oxygen species (ROS) production, propidium iodide (PI) uptake, nuclear structure change, and acidic vesicles in a p53-independent manner in p53-null HCT116 cells through fluorescence microscopy analysis of DCF/PI-, DAPI-, and AO-stained cells. The pKAL-induced anticancer effects were found to be significantly higher in p53-wild HCT116 cells than in p53-null by hematoxylin staining, CCK-8 assay, Western blot, and flow cytometric analysis of annexin V/PI-stained cells. In addition, expression of ectopic p53 in p53-null cells was upregulated by pKAL in both the nucleus and cytoplasm, increasing pKAL-induced cell death. Moreover, Western bot analysis revealed that pKAL-induced cell death was associated with upregulation of p53-dependent targets such as p21, Bax and DR5 and cleavage of PARP1 and lamin A/C in p53-wild HCT116 cells, but not in p53-null. Taken together, these results indicate that p53 plays an important role in enhancing the anticancer effects of pKAL by upregulating p53 downstream targets and inducing intracellular cell death processes.
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spelling pubmed-77304142020-12-12 p53 Enhances Artemisia annua L. Polyphenols-Induced Cell Death Through Upregulation of p53-Dependent Targets and Cleavage of PARP1 and Lamin A/C in HCT116 Colorectal Cancer Cells Jung, Eun Joo Lee, Won Sup Paramanantham, Anjugam Kim, Hye Jung Shin, Sung Chul Kim, Gon Sup Jung, Jin-Myung Ryu, Chung Ho Hong, Soon Chan Chung, Ky Hyun Kim, Choong Won Int J Mol Sci Article Plant-derived natural polyphenols exhibit anticancer activity without showing any noticeable toxicities to normal cells. The aim of this study was to investigate the role of p53 on the anticancer effect of polyphenols isolated from Korean Artemisia annua L. (pKAL) in HCT116 human colorectal cancer cells. We confirmed that pKAL induced reactive oxygen species (ROS) production, propidium iodide (PI) uptake, nuclear structure change, and acidic vesicles in a p53-independent manner in p53-null HCT116 cells through fluorescence microscopy analysis of DCF/PI-, DAPI-, and AO-stained cells. The pKAL-induced anticancer effects were found to be significantly higher in p53-wild HCT116 cells than in p53-null by hematoxylin staining, CCK-8 assay, Western blot, and flow cytometric analysis of annexin V/PI-stained cells. In addition, expression of ectopic p53 in p53-null cells was upregulated by pKAL in both the nucleus and cytoplasm, increasing pKAL-induced cell death. Moreover, Western bot analysis revealed that pKAL-induced cell death was associated with upregulation of p53-dependent targets such as p21, Bax and DR5 and cleavage of PARP1 and lamin A/C in p53-wild HCT116 cells, but not in p53-null. Taken together, these results indicate that p53 plays an important role in enhancing the anticancer effects of pKAL by upregulating p53 downstream targets and inducing intracellular cell death processes. MDPI 2020-12-07 /pmc/articles/PMC7730414/ /pubmed/33297377 http://dx.doi.org/10.3390/ijms21239315 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Jung, Eun Joo
Lee, Won Sup
Paramanantham, Anjugam
Kim, Hye Jung
Shin, Sung Chul
Kim, Gon Sup
Jung, Jin-Myung
Ryu, Chung Ho
Hong, Soon Chan
Chung, Ky Hyun
Kim, Choong Won
p53 Enhances Artemisia annua L. Polyphenols-Induced Cell Death Through Upregulation of p53-Dependent Targets and Cleavage of PARP1 and Lamin A/C in HCT116 Colorectal Cancer Cells
title p53 Enhances Artemisia annua L. Polyphenols-Induced Cell Death Through Upregulation of p53-Dependent Targets and Cleavage of PARP1 and Lamin A/C in HCT116 Colorectal Cancer Cells
title_full p53 Enhances Artemisia annua L. Polyphenols-Induced Cell Death Through Upregulation of p53-Dependent Targets and Cleavage of PARP1 and Lamin A/C in HCT116 Colorectal Cancer Cells
title_fullStr p53 Enhances Artemisia annua L. Polyphenols-Induced Cell Death Through Upregulation of p53-Dependent Targets and Cleavage of PARP1 and Lamin A/C in HCT116 Colorectal Cancer Cells
title_full_unstemmed p53 Enhances Artemisia annua L. Polyphenols-Induced Cell Death Through Upregulation of p53-Dependent Targets and Cleavage of PARP1 and Lamin A/C in HCT116 Colorectal Cancer Cells
title_short p53 Enhances Artemisia annua L. Polyphenols-Induced Cell Death Through Upregulation of p53-Dependent Targets and Cleavage of PARP1 and Lamin A/C in HCT116 Colorectal Cancer Cells
title_sort p53 enhances artemisia annua l. polyphenols-induced cell death through upregulation of p53-dependent targets and cleavage of parp1 and lamin a/c in hct116 colorectal cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7730414/
https://www.ncbi.nlm.nih.gov/pubmed/33297377
http://dx.doi.org/10.3390/ijms21239315
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