Caffeine inhibits cell proliferation and regulates PKA/GSK3ß pathways in U87MG human glioma cells.

Molecules and cells

PubMedID: 21229324

Ku BM, Lee YK, Jeong JY, Ryu J, Choi J, Kim JS, Cho YW, Roh GS, Kim HJ, Cho GJ, Choi WS, Kang SS. Caffeine inhibits cell proliferation and regulates PKA/GSK3ß pathways in U87MG human glioma cells. Mol Cells. 2011;31(3):275-9.
Caffeine is the most commonly ingested methylxanthine and has anti-cancer effects in several types of cancer. In this study, we examined the anti-cancer effects of caffeine on gliomas, both in vitro and in vivo. In vitro, caffeine treatment reduced glioma cell proliferation through G(0)/G(1)-phase cell cycle arrest by suppressing Rb phosphorylation. In addition, caffeine induced apoptosis through caspase-3 activation and poly(ADP-ribose) polymerase (PARP) cleavage. Caffeine also phosphorylated serine 9 of glycogen synthase kinase 3 beta (GSK3ß). Pretreatment with H89, a pharmacological inhibitor of protein kinase A (PKA), was able to antagonize caffeine-induced GSK3ß(ser9) phosphorylation, suggesting that the mechanism might involve a cAMP-dependent PKA-dependent pathway. In vivo, caffeine-treated tumors exhibited reduced proliferation and increased apoptosis compared with vehicle-treated tumors. These results suggest that caffeine induces cell cycle arrest and caspase-dependent cell death in glioma cells, supporting its potential use in chemotherapeutic options for malignant gliomas.