2α-Hydroxyeudesma-4,11(13)-Dien-8β,12-Olide Isolated from <i>Inula britannica</i> Induces Apoptosis in Diffuse Large B-cell Lymphoma Cells

2&#945;-Hydroxyeudesma-4,11(13)-dien-8&#946;,12-olide (HEDO), a eudesmane-type sesquiterpene lactone belonging to large group of plant terpenoids isolated from <i>Inula britannica</i>, displays cytotoxic activity against diffuse large B cell lymphoma cells in vitro. However, the...

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Main Authors: Dae Kil Jang, Ik-Soo Lee, Han-Seung Shin, Hee Min Yoo
Format: Article
Language:English
Published: MDPI AG 2020-02-01
Series:Biomolecules
Subjects:
Online Access:https://www.mdpi.com/2218-273X/10/2/324
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author Dae Kil Jang
Ik-Soo Lee
Han-Seung Shin
Hee Min Yoo
author_facet Dae Kil Jang
Ik-Soo Lee
Han-Seung Shin
Hee Min Yoo
author_sort Dae Kil Jang
collection DOAJ
description 2&#945;-Hydroxyeudesma-4,11(13)-dien-8&#946;,12-olide (HEDO), a eudesmane-type sesquiterpene lactone belonging to large group of plant terpenoids isolated from <i>Inula britannica</i>, displays cytotoxic activity against diffuse large B cell lymphoma cells in vitro. However, the molecular mechanism of the anticancer effect remains unclear. In this study, we showed that HEDO inhibits cell growth by inducing apoptosis in lymphoma cell lines through its antiproliferative activity. HEDO increases the depolarization of mitochondrial membrane potential and upregulated intracellular reactive oxygen species (ROS). Furthermore, we examined the cell cycle effect, and our results provided evidence that the arrest of the cell cycle at the SubG0/G1 phase plays an important role in the ability of HEDO to inhibit cell growth in Ontario Cancer Institute (OCI)-LY3 lymphoma cells by preventing nuclear factor-kappa B (NF-&#954;B) signaling. In addition, HEDO induced apoptosis by instigating the activation of Bcl-2-associated X (BAX) and cleaved caspase-3, decreasing B-cell lymphoma 2 (BCL2), B-cell lymphoma-extra large (BCL-XL), and procaspase 3 expression levels. Based on these findings, we suggest that HEDO has potential as an anticancer drug of lymphoma by inducing ROS-dependent accumulation of SubG0/G1 arrest and apoptosis in OCI-LY3 cells.
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spelling doaj.art-a7b5a70f48184be7aa8ef7623c9831ac2022-12-22T00:51:59ZengMDPI AGBiomolecules2218-273X2020-02-0110232410.3390/biom10020324biom100203242α-Hydroxyeudesma-4,11(13)-Dien-8β,12-Olide Isolated from <i>Inula britannica</i> Induces Apoptosis in Diffuse Large B-cell Lymphoma CellsDae Kil Jang0Ik-Soo Lee1Han-Seung Shin2Hee Min Yoo3Department of Food Science and Biotechnology, Dongguk University, Seoul 10326, KoreaHerbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, KoreaDepartment of Food Science and Biotechnology, Dongguk University, Seoul 10326, KoreaCenter for Bioanalysis, Korea Research Institute of Standards and Science (KRISS), Daejeon 34113, Korea2&#945;-Hydroxyeudesma-4,11(13)-dien-8&#946;,12-olide (HEDO), a eudesmane-type sesquiterpene lactone belonging to large group of plant terpenoids isolated from <i>Inula britannica</i>, displays cytotoxic activity against diffuse large B cell lymphoma cells in vitro. However, the molecular mechanism of the anticancer effect remains unclear. In this study, we showed that HEDO inhibits cell growth by inducing apoptosis in lymphoma cell lines through its antiproliferative activity. HEDO increases the depolarization of mitochondrial membrane potential and upregulated intracellular reactive oxygen species (ROS). Furthermore, we examined the cell cycle effect, and our results provided evidence that the arrest of the cell cycle at the SubG0/G1 phase plays an important role in the ability of HEDO to inhibit cell growth in Ontario Cancer Institute (OCI)-LY3 lymphoma cells by preventing nuclear factor-kappa B (NF-&#954;B) signaling. In addition, HEDO induced apoptosis by instigating the activation of Bcl-2-associated X (BAX) and cleaved caspase-3, decreasing B-cell lymphoma 2 (BCL2), B-cell lymphoma-extra large (BCL-XL), and procaspase 3 expression levels. Based on these findings, we suggest that HEDO has potential as an anticancer drug of lymphoma by inducing ROS-dependent accumulation of SubG0/G1 arrest and apoptosis in OCI-LY3 cells.https://www.mdpi.com/2218-273X/10/2/324<i>inula britannica</i>sesquiterpene lactonelymphomaapoptosisros
spellingShingle Dae Kil Jang
Ik-Soo Lee
Han-Seung Shin
Hee Min Yoo
2α-Hydroxyeudesma-4,11(13)-Dien-8β,12-Olide Isolated from <i>Inula britannica</i> Induces Apoptosis in Diffuse Large B-cell Lymphoma Cells
Biomolecules
<i>inula britannica</i>
sesquiterpene lactone
lymphoma
apoptosis
ros
title 2α-Hydroxyeudesma-4,11(13)-Dien-8β,12-Olide Isolated from <i>Inula britannica</i> Induces Apoptosis in Diffuse Large B-cell Lymphoma Cells
title_full 2α-Hydroxyeudesma-4,11(13)-Dien-8β,12-Olide Isolated from <i>Inula britannica</i> Induces Apoptosis in Diffuse Large B-cell Lymphoma Cells
title_fullStr 2α-Hydroxyeudesma-4,11(13)-Dien-8β,12-Olide Isolated from <i>Inula britannica</i> Induces Apoptosis in Diffuse Large B-cell Lymphoma Cells
title_full_unstemmed 2α-Hydroxyeudesma-4,11(13)-Dien-8β,12-Olide Isolated from <i>Inula britannica</i> Induces Apoptosis in Diffuse Large B-cell Lymphoma Cells
title_short 2α-Hydroxyeudesma-4,11(13)-Dien-8β,12-Olide Isolated from <i>Inula britannica</i> Induces Apoptosis in Diffuse Large B-cell Lymphoma Cells
title_sort 2α hydroxyeudesma 4 11 13 dien 8β 12 olide isolated from i inula britannica i induces apoptosis in diffuse large b cell lymphoma cells
topic <i>inula britannica</i>
sesquiterpene lactone
lymphoma
apoptosis
ros
url https://www.mdpi.com/2218-273X/10/2/324
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