Aviculin Isolated from <i>Lespedeza cuneata</i> Induce Apoptosis in Breast Cancer Cells through Mitochondria-Mediated Caspase Activation Pathway

The global incidence of breast cancer has increased. However, there are many impediments to the development of safe and effective anticancer drugs. The aim of the present study was to evaluate the effect of aviculin isolated from <i>Lespedeza cuneata</i> (Dum. Cours.) G. Don. (Fabaceae)...

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Main Authors: Dahae Lee, Yong Hoon Lee, Kwang Ho Lee, Bum Soo Lee, Akida Alishir, Yoon-Joo Ko, Ki Sung Kang, Ki Hyun Kim
Format: Article
Language:English
Published: MDPI AG 2020-04-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/25/7/1708
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author Dahae Lee
Yong Hoon Lee
Kwang Ho Lee
Bum Soo Lee
Akida Alishir
Yoon-Joo Ko
Ki Sung Kang
Ki Hyun Kim
author_facet Dahae Lee
Yong Hoon Lee
Kwang Ho Lee
Bum Soo Lee
Akida Alishir
Yoon-Joo Ko
Ki Sung Kang
Ki Hyun Kim
author_sort Dahae Lee
collection DOAJ
description The global incidence of breast cancer has increased. However, there are many impediments to the development of safe and effective anticancer drugs. The aim of the present study was to evaluate the effect of aviculin isolated from <i>Lespedeza cuneata</i> (Dum. Cours.) G. Don. (Fabaceae) on MCF-7 human breast cancer cells and determine the underlying mechanism. Using the bioassay-guided isolation by water soluble tetrazolium salt (WST-1)-based Ez-Cytox assay, nine compounds (four lignan glycosides (<b>1</b>–<b>4</b>), three flavonoid glycosides (<b>5</b>–<b>7</b>), and two phenolic compounds (<b>8</b> and <b>9</b>)) were isolated from the ethyl acetate (EA) fraction of the <i>L. cuneata</i> methanolic extract. Of these, aviculin (<b>2</b>), a lignan glycoside, was the only compound that reduced metabolic activity on MCF-7 cells below 50% (IC<sub>50</sub>: 75.47 ± 2.23 μM). The underlying mechanism was analyzed using the annexin V Alexa Fluor 488 binding assay and Western blotting. Aviculin (<b>2</b>) was found to induce apoptotic cell death through the intrinsic apoptosis pathway, as indicated by the increased expression of initiator caspase-9, executioner caspase-7, and poly (ADP-ribose) polymerase (PARP). Aviculin (<b>2</b>)-induced apoptotic cell death was accompanied by an increase in the Bax/Bcl-2 ratio. These findings demonstrated that aviculin (<b>2</b>) could induce breast cancer cell apoptosis through the intrinsic apoptosis pathway, and it can therefore be considered an excellent candidate for herbal treatment of breast cancer.
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spelling doaj.art-6bb6534d3c47484e9fa14a2b165dd89b2023-11-19T21:01:13ZengMDPI AGMolecules1420-30492020-04-01257170810.3390/molecules25071708Aviculin Isolated from <i>Lespedeza cuneata</i> Induce Apoptosis in Breast Cancer Cells through Mitochondria-Mediated Caspase Activation PathwayDahae Lee0Yong Hoon Lee1Kwang Ho Lee2Bum Soo Lee3Akida Alishir4Yoon-Joo Ko5Ki Sung Kang6Ki Hyun Kim7College of Korean Medicine, Gachon University, Seongnam 13120, KoreaSchool of Pharmacy, Sungkyunkwan University, Suwon 16419, KoreaSchool of Pharmacy, Sungkyunkwan University, Suwon 16419, KoreaSchool of Pharmacy, Sungkyunkwan University, Suwon 16419, KoreaSchool of Pharmacy, Sungkyunkwan University, Suwon 16419, KoreaLaboratory of Nuclear Magnetic Resonance, National Center for Inter-University Research Facilities (NCIRF), Seoul National University, Gwanak-gu, Seoul 08826, KoreaCollege of Korean Medicine, Gachon University, Seongnam 13120, KoreaSchool of Pharmacy, Sungkyunkwan University, Suwon 16419, KoreaThe global incidence of breast cancer has increased. However, there are many impediments to the development of safe and effective anticancer drugs. The aim of the present study was to evaluate the effect of aviculin isolated from <i>Lespedeza cuneata</i> (Dum. Cours.) G. Don. (Fabaceae) on MCF-7 human breast cancer cells and determine the underlying mechanism. Using the bioassay-guided isolation by water soluble tetrazolium salt (WST-1)-based Ez-Cytox assay, nine compounds (four lignan glycosides (<b>1</b>–<b>4</b>), three flavonoid glycosides (<b>5</b>–<b>7</b>), and two phenolic compounds (<b>8</b> and <b>9</b>)) were isolated from the ethyl acetate (EA) fraction of the <i>L. cuneata</i> methanolic extract. Of these, aviculin (<b>2</b>), a lignan glycoside, was the only compound that reduced metabolic activity on MCF-7 cells below 50% (IC<sub>50</sub>: 75.47 ± 2.23 μM). The underlying mechanism was analyzed using the annexin V Alexa Fluor 488 binding assay and Western blotting. Aviculin (<b>2</b>) was found to induce apoptotic cell death through the intrinsic apoptosis pathway, as indicated by the increased expression of initiator caspase-9, executioner caspase-7, and poly (ADP-ribose) polymerase (PARP). Aviculin (<b>2</b>)-induced apoptotic cell death was accompanied by an increase in the Bax/Bcl-2 ratio. These findings demonstrated that aviculin (<b>2</b>) could induce breast cancer cell apoptosis through the intrinsic apoptosis pathway, and it can therefore be considered an excellent candidate for herbal treatment of breast cancer.https://www.mdpi.com/1420-3049/25/7/1708<i>Lespedeza cuneata</i>aviculinMCF-7 human breast cancer cellsapoptosiscaspase
spellingShingle Dahae Lee
Yong Hoon Lee
Kwang Ho Lee
Bum Soo Lee
Akida Alishir
Yoon-Joo Ko
Ki Sung Kang
Ki Hyun Kim
Aviculin Isolated from <i>Lespedeza cuneata</i> Induce Apoptosis in Breast Cancer Cells through Mitochondria-Mediated Caspase Activation Pathway
Molecules
<i>Lespedeza cuneata</i>
aviculin
MCF-7 human breast cancer cells
apoptosis
caspase
title Aviculin Isolated from <i>Lespedeza cuneata</i> Induce Apoptosis in Breast Cancer Cells through Mitochondria-Mediated Caspase Activation Pathway
title_full Aviculin Isolated from <i>Lespedeza cuneata</i> Induce Apoptosis in Breast Cancer Cells through Mitochondria-Mediated Caspase Activation Pathway
title_fullStr Aviculin Isolated from <i>Lespedeza cuneata</i> Induce Apoptosis in Breast Cancer Cells through Mitochondria-Mediated Caspase Activation Pathway
title_full_unstemmed Aviculin Isolated from <i>Lespedeza cuneata</i> Induce Apoptosis in Breast Cancer Cells through Mitochondria-Mediated Caspase Activation Pathway
title_short Aviculin Isolated from <i>Lespedeza cuneata</i> Induce Apoptosis in Breast Cancer Cells through Mitochondria-Mediated Caspase Activation Pathway
title_sort aviculin isolated from i lespedeza cuneata i induce apoptosis in breast cancer cells through mitochondria mediated caspase activation pathway
topic <i>Lespedeza cuneata</i>
aviculin
MCF-7 human breast cancer cells
apoptosis
caspase
url https://www.mdpi.com/1420-3049/25/7/1708
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