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

Abstract

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.

Immunomodulatory Properties of Pomegranate Peel Extract in a Model of Human Peripheral Blood Mononuclear Cell Culture

“…Apoptosis and autophagy can be synergistic or opposite processes because a complex interplay between them exists at different signaling levels. For example, punicalagin exerts the cytotoxic effect 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 in human NB4 and MOLT-4 leukemia cell lines [68]. Punicalagin induces apoptotic and autophagic cell death in human U87MG glioma cells [69].…”

In vitro studies for antiparasitic activities of Punica granatum extract

“…Additionally, P. granatum' cytotoxic effects are brought on their physiochemical interaction with intracellular genetic materials (Khan et al, 2021). Previous studies suggests that P. granatum' cytotoxic effect may possibly be brought about by the stimulation of apoptosis (Cheshomi et al, 2022;Mollaei et al, 2022;Subkorn et al, 2021;Teniente et al, 2023;Turrini et al, 2015).…”

Unravelling the In Vitro and In Vivo Anti-Helicobacter pylori Effect of Delphinidin-3-O-Glucoside Rich Extract from Pomegranate Exocarp: Enhancing Autophagy and Downregulating TNF-α and COX2

“…However, continuous prolonged exposure to H. pylori decreases autophagy by inhibiting maturation of the autophagosome. Additionally, Subkorn et al [ 14 ] indicated that punicalagin (a pomegranate compound) can induce autophagy in acute leukemia. Moreover, another study by Zhang et al [ 15 ] showed that, urolithin A (a pomegranate metabolite) activates autophagy in pancreatic β-cells.…”

“…Pomegranate fruit ( Punica granatum L., family Lythraceae) is rich in polyphenolic compounds and anthocyanins and has antioxidant, anticancer, anti-inflammatory, and antiulcer activities [ 10 , 11 , 12 , 13 ]. Intriguingly, punicalagin (a pomegranate constituent) and urolithin (a pomegranate metabolite), can induce autophagy in acute leukemia [ 14 ] and pancreatic β cells [ 15 ]. Pomegranate total peel extract demonstrated anti- helicobacter effect in vitro and in vivo [ 16 ].…”