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

PeerJ

article

Paweena Subkorn¹  Chosita Norkaew¹  Kamolchanok Deesrisak¹  Dalina Tanyong¹ 

[1] Department of Clinical Microscopy, Faculty of Medical Technology, Mahidol University

关键词: Punicalagin;    Apoptosis;    Autophagy;    Leukemia;    Pomegranate;   

DOI  :  10.7717/peerj.12303

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

BackgroundPunicalagin 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.MethodsLeukemic 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.ResultsResults 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.ConclusionsThese 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.

【 授权许可】

CC BY