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Aviculin Isolated from Lespedeza cuneata Induce Apoptosis in Breast Cancer Cells through Mitochondria-Mediated Caspase Activation Pathway.

ABSTRACT: 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 Lespedeza cuneata (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 (1-4), three flavonoid glycosides (5-7), and two phenolic compounds (8 and 9)) were isolated from the ethyl acetate (EA) fraction of the L. cuneata methanolic extract. Of these, aviculin (2), a lignan glycoside, was the only compound that reduced metabolic activity on MCF-7 cells below 50% (IC50: 75.47 ± 2.23 ?M). The underlying mechanism was analyzed using the annexin V Alexa Fluor 488 binding assay and Western blotting. Aviculin (2) 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 (2)-induced apoptotic cell death was accompanied by an increase in the Bax/Bcl-2 ratio. These findings demonstrated that aviculin (2) 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.

SUBMITTER: Lee D

PROVIDER: S-EPMC7180549 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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

Lee Dahae D Lee Yong Hoon YH Lee Kwang Ho KH Lee Bum Soo BS Alishir Akida A Ko Yoon-Joo YJ Kang Ki Sung KS Kim Ki Hyun KH

Molecules (Basel, Switzerland) 20200408 7

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 glycoside ...[more]

PMID: 32276430

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Project description:BackgroundCentratherum anthelminticum (L.) seeds (CA) is a well known medicinal herb in Indian sub-continent. We recently reported anti-oxidant property of chloroform fraction of Centratherum anthelminticum (L.) seeds (CACF) by inhibiting tumor necrosis factor-? (TNF-?)-induced growth of human breast cancer cells. However, the active compounds in CACF have not been investigated previously.Methodology/principal findingsIn this study, we showed that CACF inhibited growth of MCF-7 human breast cancer cells. CACF induced apoptosis in MCF-7 cells as marked by cell size shrinkage, deformed cytoskeletal structure and DNA fragmentation. To identify the cytotoxic compound, CACF was subjected to bioassay-guided fractionation which yielded 6 fractions. CACF fraction A and B (CACF-A, -B) demonstrated highest activity among all the fractions. Further HPLC isolation, NMR and LC-MS analysis of CACF-A led to identification of vernodalin as the cytotoxic agent in CACF-A, and -B. 12,13-dihydroxyoleic acid, another major compound in CACF-C fraction was isolated for the first time from Centratherum anthelminticum (L.) seeds but showed no cytotoxic effect against MCF-7 cells. Vernodalin inhibited cell growth of human breast cancer cells MCF-7 and MDA-MB-231 by induction of cell cycle arrest and apoptosis. Increased of reactive oxygen species (ROS) production, coupled with downregulation of anti-apoptotic molecules (Bcl-2, Bcl-xL) led to reduction of mitochondrial membrane potential (MMP) and release of cytochrome c in both human breast cancer cells treated with vernodalin. Release of cytochrome c from mitochondria to cytosol triggered activation of caspase cascade, PARP cleavage, DNA damage and eventually cell death.Conclusions/significanceTo the best of our knowledge, this is the first comprehensive study on cytotoxic and apoptotic mechanism of vernodalin isolated from the Centratherum anthelminticum (L.) seeds in human breast cancer cells. Overall, our data suggest a potential therapeutic value of vernodalin to be further developed as new anti-cancer drug.

Dataset Information

Aviculin Isolated from Lespedeza cuneata Induce Apoptosis in Breast Cancer Cells through Mitochondria-Mediated Caspase Activation Pathway.

Publications

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

Similar Datasets

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