Punicalagin, a pomegranate compound, induces apoptosis and autophagy in acute leukemia

Background Punicalagin is the major phenolic compound found in pomegranate peels. It has several reported medical benefits, including antioxidant, anti-inflammatory, and anticancer properties. The present study investigated the anti-leukemic effects and the molecular mechanism of punicalagin on NB4...

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Autores principales:	Paweena Subkorn, Chosita Norkaew, Kamolchanok Deesrisak, Dalina Tanyong
Formato:	article
Lenguaje:	EN
Publicado:	PeerJ Inc. 2021
Materias:	Punicalagin Apoptosis Autophagy Leukemia Pomegranate Medicine R
Acceso en línea:	https://doaj.org/article/f7a6fa724098455daf962d19892a6cb8
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spelling	oai:doaj.org-article:f7a6fa724098455daf962d19892a6cb82021-11-04T15:05:12ZPunicalagin, a pomegranate compound, induces apoptosis and autophagy in acute leukemia10.7717/peerj.123032167-8359https://doaj.org/article/f7a6fa724098455daf962d19892a6cb82021-11-01T00:00:00Zhttps://peerj.com/articles/12303.pdfhttps://peerj.com/articles/12303/https://doaj.org/toc/2167-8359Background Punicalagin is the major phenolic compound found in pomegranate peels. It has several reported medical benefits, including antioxidant, anti-inflammatory, and anticancer properties. The present study investigated the anti-leukemic effects and the molecular mechanism of punicalagin on NB4 and MOLT-4 leukemic cell lines. Methods Leukemic cells were treated with punicalagin and cell viability was determined using MTS assay. Apoptosis and autophagy were analyzed by flow cytometry using Annexin V-FITC/PI and anti-LC3/FITC antibodies staining, respectively. Apoptotic and autophagic mRNA expression were determined using reverse transcription-quantitative PCR. STITCH bioinformatics tools were used to predict the interaction between punicalagin and its proposed target proteins. Results Results indicated that punicalagin decreased NB4 and MOLT-4 cell viability in a dose-dependent manner. Punicalagin, in combination with daunorubicin, exhibited synergistic cytotoxic effects. Punicalagin induced apoptosis through the upregulation of caspase-3/-8/-9, Bax and the downregulation of Bcl-2 expression. Punicalagin also promoted autophagy via the downregulation of mTOR and the upregulation of ULK1 expression. Cyclooxygenase-2 and toll-like receptor 4 were found to be involved in punicalagin-induced cell death in punicalagin-targeted protein interactions. Conclusions These results suggest that punicalagin exerts cytotoxic activities by suppressing proliferation and promoting apoptosis and autophagy by activating the caspase cascade, altering Bax and Bcl-2, and regulating autophagy via mTOR/ULK1 signaling.Paweena SubkornChosita NorkaewKamolchanok DeesrisakDalina TanyongPeerJ Inc.articlePunicalaginApoptosisAutophagyLeukemiaPomegranateMedicineRENPeerJ, Vol 9, p e12303 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Punicalagin Apoptosis Autophagy Leukemia Pomegranate Medicine R
spellingShingle	Punicalagin Apoptosis Autophagy Leukemia Pomegranate Medicine R Paweena Subkorn Chosita Norkaew Kamolchanok Deesrisak Dalina Tanyong Punicalagin, a pomegranate compound, induces apoptosis and autophagy in acute leukemia
description	Background Punicalagin is the major phenolic compound found in pomegranate peels. It has several reported medical benefits, including antioxidant, anti-inflammatory, and anticancer properties. The present study investigated the anti-leukemic effects and the molecular mechanism of punicalagin on NB4 and MOLT-4 leukemic cell lines. Methods Leukemic cells were treated with punicalagin and cell viability was determined using MTS assay. Apoptosis and autophagy were analyzed by flow cytometry using Annexin V-FITC/PI and anti-LC3/FITC antibodies staining, respectively. Apoptotic and autophagic mRNA expression were determined using reverse transcription-quantitative PCR. STITCH bioinformatics tools were used to predict the interaction between punicalagin and its proposed target proteins. Results Results indicated that punicalagin decreased NB4 and MOLT-4 cell viability in a dose-dependent manner. Punicalagin, in combination with daunorubicin, exhibited synergistic cytotoxic effects. Punicalagin induced apoptosis through the upregulation of caspase-3/-8/-9, Bax and the downregulation of Bcl-2 expression. Punicalagin also promoted autophagy via the downregulation of mTOR and the upregulation of ULK1 expression. Cyclooxygenase-2 and toll-like receptor 4 were found to be involved in punicalagin-induced cell death in punicalagin-targeted protein interactions. Conclusions These results suggest that punicalagin exerts cytotoxic activities by suppressing proliferation and promoting apoptosis and autophagy by activating the caspase cascade, altering Bax and Bcl-2, and regulating autophagy via mTOR/ULK1 signaling.
format	article
author	Paweena Subkorn Chosita Norkaew Kamolchanok Deesrisak Dalina Tanyong
author_facet	Paweena Subkorn Chosita Norkaew Kamolchanok Deesrisak Dalina Tanyong
author_sort	Paweena Subkorn
title	Punicalagin, a pomegranate compound, induces apoptosis and autophagy in acute leukemia
title_short	Punicalagin, a pomegranate compound, induces apoptosis and autophagy in acute leukemia
title_full	Punicalagin, a pomegranate compound, induces apoptosis and autophagy in acute leukemia
title_fullStr	Punicalagin, a pomegranate compound, induces apoptosis and autophagy in acute leukemia
title_full_unstemmed	Punicalagin, a pomegranate compound, induces apoptosis and autophagy in acute leukemia
title_sort	punicalagin, a pomegranate compound, induces apoptosis and autophagy in acute leukemia
publisher	PeerJ Inc.
publishDate	2021
url	https://doaj.org/article/f7a6fa724098455daf962d19892a6cb8
work_keys_str_mv	AT paweenasubkorn punicalaginapomegranatecompoundinducesapoptosisandautophagyinacuteleukemia AT chositanorkaew punicalaginapomegranatecompoundinducesapoptosisandautophagyinacuteleukemia AT kamolchanokdeesrisak punicalaginapomegranatecompoundinducesapoptosisandautophagyinacuteleukemia AT dalinatanyong punicalaginapomegranatecompoundinducesapoptosisandautophagyinacuteleukemia
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Punicalagin, a pomegranate compound, induces apoptosis and autophagy in acute leukemia

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