Department of Immunology, Keimyung University, Jung-Gu, Taegu, South Korea.
Apoptosis. 2009 Nov;14(11):1378-86. doi: 10.1007/s10495-009-0407-x.
Kahweol, the coffee-specific diterpene, has been reported for its tumor cell growth inhibitory activity and anti-carcinogenic activity. The mechanism by which kahweol initiates apoptosis remains poorly understood. In the present study, we investigated the effect of kahweol on the apoptotic pathway in U937 human promonocytic cells. We show that kahweol induces apoptosis in association with the activation of caspase 3 and cytochrome c release from the mitochondria to the cytosol, as well as down-regulation of anti-apoptotic proteins (Bcl-2, Bcl-xL, Mcl-1 and XIAP). Kahweol altered the phosphorylation state of members of the MAPKs and Akt. Ectopic expression of Bcl-2 or constitutive active Akt (myr-Akt) in U937 cells attenuates kahweol-induced apoptosis. In addition, we have also shown that JNK and Akt signal pathway plays a crucial role in kahweol-induced apoptosis in U937 cells. Taken together, our results show the activity of kahweol to modulate multiple components in apoptotic response of human leukemia cells and raise the possibility a novel therapeutic strategy in hematological malignancies.
卡瓦醇是一种咖啡特有的二萜类化合物，具有抑制肿瘤细胞生长和抗癌活性。卡瓦醇引发细胞凋亡的机制尚不清楚。在本研究中，我们研究了卡瓦醇对 U937 人单核白血病细胞凋亡途径的影响。结果表明，卡瓦醇诱导细胞凋亡与 caspase-3 的激活以及线粒体细胞色素 c 向细胞质的释放有关，同时下调抗凋亡蛋白（Bcl-2、Bcl-xL、Mcl-1 和 XIAP）。卡瓦醇改变了 MAPKs 和 Akt 家族成员的磷酸化状态。在 U937 细胞中转染 Bcl-2 或组成性激活 Akt（myr-Akt）可减弱卡瓦醇诱导的细胞凋亡。此外，我们还表明 JNK 和 Akt 信号通路在卡瓦醇诱导的 U937 细胞凋亡中发挥关键作用。综上所述，我们的结果表明卡瓦醇能够调节人白血病细胞凋亡反应中的多个成分，为血液系统恶性肿瘤提供了一种新的治疗策略的可能性。
