Punicalagin induces apoptotic and autophagic cell death in human U87MG glioma cells

Shyang Guang Wang, Ming Hung Huang, Jui Hsiang Li, Fu I. Lai, Horng Mo Lee, Yuan Nian Hsu

Research output: Contribution to journalArticle

35 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1411-1419
Number of pages9
JournalActa Pharmacologica Sinica
Volume34
Issue number11
DOIs
Publication statusPublished - Nov 2013

Keywords

  • AMPK
  • Apoptosis
  • Autophagy
  • Chloroquine
  • Human glioma
  • Microtubule-associated protein light chain 3
  • P27
  • Punicalagin
  • Z-DEVD-fmk

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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    Wang, S. G., Huang, M. H., Li, J. H., Lai, F. I., Lee, H. M., & Hsu, Y. N. (2013). Punicalagin induces apoptotic and autophagic cell death in human U87MG glioma cells. Acta Pharmacologica Sinica, 34(11), 1411-1419. https://doi.org/10.1038/aps.2013.98