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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2020-04-01
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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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