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ROS-Mediated Anti-Tumor Effect of Coptidis Rhizoma against Human Hepatocellular Carcinoma Hep3B Cells and Xenografts

Coptidis Rhizoma is the dried rhizome from the Coptis chinensis Franch. that has been shown to have a number of beneficial pharmacological properties including antioxidant, anti-inflammatory, and anti-cancer effects. However, the anti-cancer effects of Coptidis Rhizoma on hepatocellular carcinoma (H...

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Autores principales: Kim, So Young, Park, Cheol, Kim, Min Yeong, Ji, Seon Yeong, Hwangbo, Hyun, Lee, Hyesook, Hong, Su Hyun, Han, Min Ho, Jeong, Jin-Woo, Kim, Gi-Young, Son, Chang-Gue, Cheong, JaeHun, Choi, Yung Hyun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8124566/
https://www.ncbi.nlm.nih.gov/pubmed/33946527
http://dx.doi.org/10.3390/ijms22094797
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author Kim, So Young
Park, Cheol
Kim, Min Yeong
Ji, Seon Yeong
Hwangbo, Hyun
Lee, Hyesook
Hong, Su Hyun
Han, Min Ho
Jeong, Jin-Woo
Kim, Gi-Young
Son, Chang-Gue
Cheong, JaeHun
Choi, Yung Hyun
author_facet Kim, So Young
Park, Cheol
Kim, Min Yeong
Ji, Seon Yeong
Hwangbo, Hyun
Lee, Hyesook
Hong, Su Hyun
Han, Min Ho
Jeong, Jin-Woo
Kim, Gi-Young
Son, Chang-Gue
Cheong, JaeHun
Choi, Yung Hyun
author_sort Kim, So Young
collection PubMed
description Coptidis Rhizoma is the dried rhizome from the Coptis chinensis Franch. that has been shown to have a number of beneficial pharmacological properties including antioxidant, anti-inflammatory, and anti-cancer effects. However, the anti-cancer effects of Coptidis Rhizoma on hepatocellular carcinoma (HCC) remain unclear. In this study, we investigated the anti-cancer properties of Coptidis Rhizoma ethanol extract (CR) in HCC Hep3B cells and in a xenograft mouse model. Our results showed that the CR significantly inhibited cell growth and induced apoptosis in Hep3B cells through increased expression of Bcl-2 associated x-protein (Bax) and cleavage of poly-ADP ribose polymerase (PARP), reduced expression of Bcl-2, and activated caspases. CR also increased the generation of intracellular reactive oxygen species (ROS), which caused a loss of mitochondrial membrane potential (MMP, ΔΨm) and activation of the mitochondria-mediated intrinsic apoptosis pathway. Moreover, N-acetylcysteine (NAC), a ROS inhibitor, markedly blocked the effects of CR on apoptotic pathways. CR also induced the expression of light chain 3 (LC3)-I/II, a key autophagy regulator, whereas CR-mediated autophagy was significantly suppressed by NAC. In addition, pre-treatment with NAC perfectly attenuated the inhibition of cell invasion and migration of CR-stimulated Hep3B cells. Furthermore, oral administration of CR suppressed Hep3B tumor growth in xenograft mice without toxicity, alterations to body weight, or changes in hematological and biochemical profiles. Taken together, our findings suggest that CR has anti-tumor effects that result from ROS generation, and may be a potential pharmacological intervention for HCC.
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spelling pubmed-81245662021-05-17 ROS-Mediated Anti-Tumor Effect of Coptidis Rhizoma against Human Hepatocellular Carcinoma Hep3B Cells and Xenografts Kim, So Young Park, Cheol Kim, Min Yeong Ji, Seon Yeong Hwangbo, Hyun Lee, Hyesook Hong, Su Hyun Han, Min Ho Jeong, Jin-Woo Kim, Gi-Young Son, Chang-Gue Cheong, JaeHun Choi, Yung Hyun Int J Mol Sci Article Coptidis Rhizoma is the dried rhizome from the Coptis chinensis Franch. that has been shown to have a number of beneficial pharmacological properties including antioxidant, anti-inflammatory, and anti-cancer effects. However, the anti-cancer effects of Coptidis Rhizoma on hepatocellular carcinoma (HCC) remain unclear. In this study, we investigated the anti-cancer properties of Coptidis Rhizoma ethanol extract (CR) in HCC Hep3B cells and in a xenograft mouse model. Our results showed that the CR significantly inhibited cell growth and induced apoptosis in Hep3B cells through increased expression of Bcl-2 associated x-protein (Bax) and cleavage of poly-ADP ribose polymerase (PARP), reduced expression of Bcl-2, and activated caspases. CR also increased the generation of intracellular reactive oxygen species (ROS), which caused a loss of mitochondrial membrane potential (MMP, ΔΨm) and activation of the mitochondria-mediated intrinsic apoptosis pathway. Moreover, N-acetylcysteine (NAC), a ROS inhibitor, markedly blocked the effects of CR on apoptotic pathways. CR also induced the expression of light chain 3 (LC3)-I/II, a key autophagy regulator, whereas CR-mediated autophagy was significantly suppressed by NAC. In addition, pre-treatment with NAC perfectly attenuated the inhibition of cell invasion and migration of CR-stimulated Hep3B cells. Furthermore, oral administration of CR suppressed Hep3B tumor growth in xenograft mice without toxicity, alterations to body weight, or changes in hematological and biochemical profiles. Taken together, our findings suggest that CR has anti-tumor effects that result from ROS generation, and may be a potential pharmacological intervention for HCC. MDPI 2021-04-30 /pmc/articles/PMC8124566/ /pubmed/33946527 http://dx.doi.org/10.3390/ijms22094797 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
Kim, So Young
Park, Cheol
Kim, Min Yeong
Ji, Seon Yeong
Hwangbo, Hyun
Lee, Hyesook
Hong, Su Hyun
Han, Min Ho
Jeong, Jin-Woo
Kim, Gi-Young
Son, Chang-Gue
Cheong, JaeHun
Choi, Yung Hyun
ROS-Mediated Anti-Tumor Effect of Coptidis Rhizoma against Human Hepatocellular Carcinoma Hep3B Cells and Xenografts
title ROS-Mediated Anti-Tumor Effect of Coptidis Rhizoma against Human Hepatocellular Carcinoma Hep3B Cells and Xenografts
title_full ROS-Mediated Anti-Tumor Effect of Coptidis Rhizoma against Human Hepatocellular Carcinoma Hep3B Cells and Xenografts
title_fullStr ROS-Mediated Anti-Tumor Effect of Coptidis Rhizoma against Human Hepatocellular Carcinoma Hep3B Cells and Xenografts
title_full_unstemmed ROS-Mediated Anti-Tumor Effect of Coptidis Rhizoma against Human Hepatocellular Carcinoma Hep3B Cells and Xenografts
title_short ROS-Mediated Anti-Tumor Effect of Coptidis Rhizoma against Human Hepatocellular Carcinoma Hep3B Cells and Xenografts
title_sort ros-mediated anti-tumor effect of coptidis rhizoma against human hepatocellular carcinoma hep3b cells and xenografts
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8124566/
https://www.ncbi.nlm.nih.gov/pubmed/33946527
http://dx.doi.org/10.3390/ijms22094797
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