Department of Anatomy and Neurobiology, Institute of Health Science, School of Medicine, Gyeongsang National University, Jinju, 660-751, Korea.
Mol Cells. 2011 Mar;31(3):275-9. doi: 10.1007/s10059-011-0027-5. Epub 2010 Dec 30.
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 (GSK3β). Pretreatment with H89, a pharmacological inhibitor of protein kinase A (PKA), was able to antagonize caffeine-induced GSK3β(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.
咖啡因是最常被摄入的甲基黄嘌呤，对多种类型的癌症具有抗癌作用。在这项研究中，我们研究了咖啡因对体外和体内胶质瘤的抗癌作用。在体外，咖啡因通过抑制 Rb 磷酸化使细胞周期停滞在 G0/G1 期，从而减少神经胶质瘤细胞的增殖。此外，咖啡因通过激活半胱天冬酶-3 和聚（ADP-核糖）聚合酶（PARP）切割诱导细胞凋亡。咖啡因还磷酸化糖原合酶激酶 3β（GSK3β）的丝氨酸 9 位。用 H89（蛋白激酶 A（PKA）的药理学抑制剂）预处理能够拮抗咖啡因诱导的 GSK3β（ser9）磷酸化，表明该机制可能涉及 cAMP 依赖性 PKA 依赖性途径。在体内，与用载体处理的肿瘤相比，用咖啡因处理的肿瘤显示出增殖减少和凋亡增加。这些结果表明咖啡因诱导神经胶质瘤细胞的细胞周期停滞和半胱天冬酶依赖性细胞死亡，支持其在恶性神经胶质瘤的化学治疗选择中的潜在用途。
