Anticancer Activity of Continentalic Acid in B-Cell Lymphoma

<i>Aralia continentalis</i> 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 <i>A. continentalis</i> extract and its three diterpenes efficiently kill B-l...

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Autores principales:	Byeol-Eun Jeon, Chan-Seong Kwon, Ji-Eun Lee, Keumok Moon, Jaeho Cha, Inmyoung Park, Sara Koh, Myunghee Yoon, Sang-Woo Kim, Jeong Nam Kim
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	<i>Aralia continentalis</i> diterpenes B-cell lymphoma anti-cancer activities Organic chemistry QD241-441
Acceso en línea:	https://doaj.org/article/b3acb427821249b785f9eae5382abf53
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spelling	oai:doaj.org-article:b3acb427821249b785f9eae5382abf532021-11-25T18:27:41ZAnticancer Activity of Continentalic Acid in B-Cell Lymphoma10.3390/molecules262268451420-3049https://doaj.org/article/b3acb427821249b785f9eae5382abf532021-11-01T00:00:00Zhttps://www.mdpi.com/1420-3049/26/22/6845https://doaj.org/toc/1420-3049<i>Aralia continentalis</i> 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 <i>A. continentalis</i> 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 <i>A. continentalis</i> 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 <i>A. continentalis</i> 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.Byeol-Eun JeonChan-Seong KwonJi-Eun LeeKeumok MoonJaeho ChaInmyoung ParkSara KohMyunghee YoonSang-Woo KimJeong Nam KimMDPI AGarticle<i>Aralia continentalis</i>diterpenesB-cell lymphomaanti-cancer activitiesOrganic chemistryQD241-441ENMolecules, Vol 26, Iss 6845, p 6845 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	<i>Aralia continentalis</i> diterpenes B-cell lymphoma anti-cancer activities Organic chemistry QD241-441
spellingShingle	<i>Aralia continentalis</i> diterpenes B-cell lymphoma anti-cancer activities Organic chemistry QD241-441 Byeol-Eun Jeon Chan-Seong Kwon Ji-Eun Lee Keumok Moon Jaeho Cha Inmyoung Park Sara Koh Myunghee Yoon Sang-Woo Kim Jeong Nam Kim Anticancer Activity of Continentalic Acid in B-Cell Lymphoma
description	<i>Aralia continentalis</i> 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 <i>A. continentalis</i> 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 <i>A. continentalis</i> 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 <i>A. continentalis</i> 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.
format	article
author	Byeol-Eun Jeon Chan-Seong Kwon Ji-Eun Lee Keumok Moon Jaeho Cha Inmyoung Park Sara Koh Myunghee Yoon Sang-Woo Kim Jeong Nam Kim
author_facet	Byeol-Eun Jeon Chan-Seong Kwon Ji-Eun Lee Keumok Moon Jaeho Cha Inmyoung Park Sara Koh Myunghee Yoon Sang-Woo Kim Jeong Nam Kim
author_sort	Byeol-Eun Jeon
title	Anticancer Activity of Continentalic Acid in B-Cell Lymphoma
title_short	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_sort	anticancer activity of continentalic acid in b-cell lymphoma
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/b3acb427821249b785f9eae5382abf53
work_keys_str_mv	AT byeoleunjeon anticanceractivityofcontinentalicacidinbcelllymphoma AT chanseongkwon anticanceractivityofcontinentalicacidinbcelllymphoma AT jieunlee anticanceractivityofcontinentalicacidinbcelllymphoma AT keumokmoon anticanceractivityofcontinentalicacidinbcelllymphoma AT jaehocha anticanceractivityofcontinentalicacidinbcelllymphoma AT inmyoungpark anticanceractivityofcontinentalicacidinbcelllymphoma AT sarakoh anticanceractivityofcontinentalicacidinbcelllymphoma AT myungheeyoon anticanceractivityofcontinentalicacidinbcelllymphoma AT sangwookim anticanceractivityofcontinentalicacidinbcelllymphoma AT jeongnamkim anticanceractivityofcontinentalicacidinbcelllymphoma
_version_	1718411152840458240

Anticancer Activity of Continentalic Acid in B-Cell Lymphoma

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