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Mol. Cells 2011; 31(3): 275-279

Published online December 30, 2011

https://doi.org/10.1007/s10059-011-0027-5

© The Korean Society for Molecular and Cellular Biology

Caffeine Inhibits Cell Proliferation and Regu-lates PKA/GSK3β Pathways in U87MG Human Glioma Cells

Bo Mi Ku, Yeon Kyung Lee, Joo Yeon Jeong, Jinhyun Ryu, Jungil Choi, Joon Soo Kim1, Yong Woon Cho1, Gu Seob Roh, Hyun Joon Kim, Gyeong Jae Cho, Wan Sung Choi, and Sang Soo Kang*

Department of Anatomy and Neurobiology, Institute of Health Science, School of Medicine, Gyeongsang National University, Jinju 660-751, Korea, 1Department of Neurosurgery, Samgsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon 630-723, Korea

Correspondence to : *Correspondence: kangss@gnu.ac.kr

Received: November 12, 2010; Revised: December 7, 2010; Accepted: December 8, 2010

Abstract

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 treat-ment reduced glioma cell proliferation through G0/G1-phase cell cycle arrest by suppressing Rb phosphorylation. In addition, caffeine induced apoptosis through caspase-3 activation and poly(ADP-ribose) polymerase (PARP) clea-vage. Caffeine also phosphorylated serine 9 of glycogen synthase kinase 3 beta (GSK3β). Pretreatment with H89, a pharmacological inhibitor of protein kinase A (PKA), was able to antagonize caffeine-induced GSK3βser9 phosphory-lation, 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.

Keywords Apoptosis, caffeine, cell proliferation, Glioma, GSK3β

Article

Research Article

Mol. Cells 2011; 31(3): 275-279

Published online March 31, 2011 https://doi.org/10.1007/s10059-011-0027-5

Copyright © The Korean Society for Molecular and Cellular Biology.

Caffeine Inhibits Cell Proliferation and Regu-lates PKA/GSK3β Pathways in U87MG Human Glioma Cells

Bo Mi Ku, Yeon Kyung Lee, Joo Yeon Jeong, Jinhyun Ryu, Jungil Choi, Joon Soo Kim1, Yong Woon Cho1, Gu Seob Roh, Hyun Joon Kim, Gyeong Jae Cho, Wan Sung Choi, and Sang Soo Kang*

Department of Anatomy and Neurobiology, Institute of Health Science, School of Medicine, Gyeongsang National University, Jinju 660-751, Korea, 1Department of Neurosurgery, Samgsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon 630-723, Korea

Correspondence to:*Correspondence: kangss@gnu.ac.kr

Received: November 12, 2010; Revised: December 7, 2010; Accepted: December 8, 2010

Abstract

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 treat-ment reduced glioma cell proliferation through G0/G1-phase cell cycle arrest by suppressing Rb phosphorylation. In addition, caffeine induced apoptosis through caspase-3 activation and poly(ADP-ribose) polymerase (PARP) clea-vage. Caffeine also phosphorylated serine 9 of glycogen synthase kinase 3 beta (GSK3β). Pretreatment with H89, a pharmacological inhibitor of protein kinase A (PKA), was able to antagonize caffeine-induced GSK3βser9 phosphory-lation, 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.

Keywords: Apoptosis, caffeine, cell proliferation, Glioma, GSK3β

Mol. Cells
Jan 31, 2023 Vol.46 No.1, pp. 1~67
COVER PICTURE
RNAs form diverse shapes and play multiple functions as central molecules of gene expression. In this special issue on RNA, seven minireviews illustrate how basic concepts and recent RNA biology findings are transformed into new and exciting RNA therapeutics.

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