Caffeine inhibits cell proliferation and regulates PKA/GSK3β pathways in U87MG human glioma cells
Caffeine inhibits cell proliferation and regulates PKA/GSK3β pathways in U87MG human glioma cells
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DOI：
10.1007/s10059-011-0027-5
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发表时间：
2011-03-01
影响因子：
3.8
通讯作者：
Kang, Sang Soo
中科院分区：
文献类型：
--
作者：
Ku, Bo Mi;Lee, Yeon Kyung;Kang, Sang Soo
咖啡因是最常摄入的甲基黄嘌呤，对几种类型的癌症有抗癌作用。在这项研究中，我们研究了咖啡因在体外和体内对胶质瘤的抗癌作用。在体外实验中，咖啡因通过抑制Rb蛋白磷酸化，阻滞细胞周期G（0）/G（1）期，从而减少胶质瘤细胞的增殖。此外，咖啡因通过caspase-3激活和聚（ADP-核糖）聚合酶（PARP）裂解诱导细胞凋亡。咖啡因还磷酸化糖原合成酶激酶3 β（GSK 3 β）的丝氨酸9。用蛋白激酶A（PKA）的药理学抑制剂H89预处理能够拮抗咖啡因诱导的GSK 3 β（ser 9）磷酸化，表明该机制可能涉及cAMP依赖的PKA依赖性途径。在体内，咖啡因治疗的肿瘤表现出减少的增殖和增加的凋亡相比，车辆处理的肿瘤。这些结果表明，咖啡因诱导神经胶质瘤细胞的细胞周期阻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疗选择的潜在用途。
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 (GSK3 beta). Pretreatment with H89, a pharmacological inhibitor of protein kinase A (PKA), was able to antagonize caffeine-induced GSK3 beta(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.