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Anticancer Activity of Continentalic Acid in B-Cell Lymphoma

Aralia continentalis has been used in Korea as a folk remedy for arthralgia, rheumatism, and inflammation. However, its anti-lymphoma effect remains uncharacterized. Here, we demonstrate that A. continentalis extract and its three diterpenes efficiently kill B-lymphoma cells. Our in vitro and in viv...

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Autores principales: Jeon, Byeol-Eun, Kwon, Chan-Seong, Lee, Ji-Eun, Moon, Keumok, Cha, Jaeho, Park, Inmyoung, Koh, Sara, Yoon, Myunghee, Kim, Sang-Woo, Kim, Jeong Nam
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8625780/
https://www.ncbi.nlm.nih.gov/pubmed/34833935
http://dx.doi.org/10.3390/molecules26226845
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author Jeon, Byeol-Eun
Kwon, Chan-Seong
Lee, Ji-Eun
Moon, Keumok
Cha, Jaeho
Park, Inmyoung
Koh, Sara
Yoon, Myunghee
Kim, Sang-Woo
Kim, Jeong Nam
author_facet Jeon, Byeol-Eun
Kwon, Chan-Seong
Lee, Ji-Eun
Moon, Keumok
Cha, Jaeho
Park, Inmyoung
Koh, Sara
Yoon, Myunghee
Kim, Sang-Woo
Kim, Jeong Nam
author_sort Jeon, Byeol-Eun
collection PubMed
description Aralia continentalis has been used in Korea as a folk remedy for arthralgia, rheumatism, and inflammation. However, its anti-lymphoma effect remains uncharacterized. Here, we demonstrate that A. continentalis extract and its three diterpenes efficiently kill B-lymphoma cells. Our in vitro and in vivo results suggest that the cytotoxic activities of continentalic acid, a major diterpene from A. continentalis extract, are specific towards cancer cells while leaving normal murine cells and tissues unharmed. Mechanistically, continentalic acid represses the expression of pro-survival Bcl-2 family members, such as Mcl-1 and Bcl-xL. It dissociates the mitochondrial membrane potential, leading to the stimulation of effector caspase 3/7 activities and, ultimately, cell death. Intriguingly, this agent therapeutically synergizes with roflumilast, a pan-PDE4 inhibitor that has been successfully repurposed for the treatment of aggressive B-cell malignancies in recent clinical tests. Our findings unveiled that A. continentalis extract and three of the plant’s diterpenes exhibit anti-cancer activities. We also demonstrate the synergistic inhibitory effect of continentalic acid on the survival of B-lymphoma cells when combined with roflumilast. Taken in conjunction, continentalic acid may hold significant potential for the treatment of B-cell lymphoma.
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spelling pubmed-86257802021-11-27 Anticancer Activity of Continentalic Acid in B-Cell Lymphoma Jeon, Byeol-Eun Kwon, Chan-Seong Lee, Ji-Eun Moon, Keumok Cha, Jaeho Park, Inmyoung Koh, Sara Yoon, Myunghee Kim, Sang-Woo Kim, Jeong Nam Molecules Article Aralia continentalis has been used in Korea as a folk remedy for arthralgia, rheumatism, and inflammation. However, its anti-lymphoma effect remains uncharacterized. Here, we demonstrate that A. continentalis extract and its three diterpenes efficiently kill B-lymphoma cells. Our in vitro and in vivo results suggest that the cytotoxic activities of continentalic acid, a major diterpene from A. continentalis extract, are specific towards cancer cells while leaving normal murine cells and tissues unharmed. Mechanistically, continentalic acid represses the expression of pro-survival Bcl-2 family members, such as Mcl-1 and Bcl-xL. It dissociates the mitochondrial membrane potential, leading to the stimulation of effector caspase 3/7 activities and, ultimately, cell death. Intriguingly, this agent therapeutically synergizes with roflumilast, a pan-PDE4 inhibitor that has been successfully repurposed for the treatment of aggressive B-cell malignancies in recent clinical tests. Our findings unveiled that A. continentalis extract and three of the plant’s diterpenes exhibit anti-cancer activities. We also demonstrate the synergistic inhibitory effect of continentalic acid on the survival of B-lymphoma cells when combined with roflumilast. Taken in conjunction, continentalic acid may hold significant potential for the treatment of B-cell lymphoma. MDPI 2021-11-12 /pmc/articles/PMC8625780/ /pubmed/34833935 http://dx.doi.org/10.3390/molecules26226845 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
Jeon, Byeol-Eun
Kwon, Chan-Seong
Lee, Ji-Eun
Moon, Keumok
Cha, Jaeho
Park, Inmyoung
Koh, Sara
Yoon, Myunghee
Kim, Sang-Woo
Kim, Jeong Nam
Anticancer Activity of Continentalic Acid in B-Cell Lymphoma
title Anticancer Activity of Continentalic Acid in B-Cell Lymphoma
title_full Anticancer Activity of Continentalic Acid in B-Cell Lymphoma
title_fullStr Anticancer Activity of Continentalic Acid in B-Cell Lymphoma
title_full_unstemmed Anticancer Activity of Continentalic Acid in B-Cell Lymphoma
title_short Anticancer Activity of Continentalic Acid in B-Cell Lymphoma
title_sort anticancer activity of continentalic acid in b-cell lymphoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8625780/
https://www.ncbi.nlm.nih.gov/pubmed/34833935
http://dx.doi.org/10.3390/molecules26226845
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