@article{APS4362,
author = {Shyang-guang Wang and Ming-hung Huang and Jui-hsiang Li and Fu-i Lai and Horng-mo Lee and Yuan-nian Hsu},
title = {Punicalagin induces apoptotic and autophagic cell death in human U87MG glioma cells},
journal = {Acta Pharmacologica Sinica},
volume = {34},
number = {11},
year = {2016},
keywords = {},
abstract = {Aim: To investigate the effects of punicalagin, a polyphenol isolated from Punica granatum, on human U87MG glioma cells in vitro.
Methods: The viability of human U87MG glioma cells was evaluated using MTT assay. Cell cycle was detected with flow cytometry analysis. The levels of Bcl-2, cleaved caspase-9, cleaved poly(ADP-ribose) polymerase (PARP), phosphor-AMPK and phosphor-p27 at Thr198 were measured using immunoblot analyses. Caspase-3 activity was determined with spectrophotometer. To determine autophagy, LC3 cleavage and punctate patterns were examined.
Results: Punicalagin (1-30 μg/mL) dose-dependently inhibited the cell viability in association with increased cyclin E level and decreased cyclin B and cyclin A levels. The treatment also induced apoptosis as shown by the cleavage of PARP, activation of caspase-9, and increase of caspase-3 activity in the cells. However, pretreatment of the cells with the pan-caspase inhibitor z-DEVD-fmk (50 μmol/L) did not completely prevent the cell death. On the other hand, punicalagin treatment increased LC3-II cleavage and caused GFP-LC3-II-stained punctate pattern in the cells. Suppressing autophagy of cells with chloroquine (1-10 μmol/L) dose-dependently alleviated the cell death caused by punicalagin. Punicalagin (1-30 μg/mL) also increased the levels phosphor-AMPK and phosphor-p27 at Thr198 in the cells, which were correlated with the induction of autophagic cell death.
Conclusion: Punicalagin induces human U87MG glioma cell death through both apoptotic and autophagic pathways.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/4362}
}