Resveratrol suppresses constitutive activation of AKT via generation of ROS and induces apoptosis in diffuse large B cell lymphoma cell lines.
Resveratrol suppresses constitutive activation of AKT via generation of ROS and induces apoptosis in diffuse large B cell lymphoma cell lines.
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DOI：
10.1371/journal.pone.0024703
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Al-Kuraya KS
中科院分区：
文献类型：
--
作者：
Hussain AR;Uddin S;Bu R;Khan OS;Ahmed SO;Ahmed M;Al-Kuraya KS
我们最近发现，PI3-K/AKT生存通路失控在弥漫性大B细胞淋巴瘤(DLBCL)的发病机制中起重要作用。为了寻找新的治疗药物，我们研究了白藜芦醇(反式-3，4‘，5-三羟基二苯乙烯)，一种天然存在于弥漫性大B细胞淋巴瘤(DLBCL)细胞上的多酚化合物在抑制细胞活力和诱导细胞凋亡中的作用。我们研究了白藜芦醇对DLBCL细胞的作用，发现白藜芦醇通过产生活性氧(ROS)抑制AKT及其下游靶点，从而抑制细胞活力和诱导细胞凋亡。同时，白藜芦醇处理DLBCL细胞也引起ROS依赖的DR5表达上调；有趣的是，DLBCL与亚毒性剂量的TRAIL和白藜芦醇共同处理DLBCL后，通过利用DR5协同诱导细胞凋亡，而DR5的基因沉默则取消了这一作用。总之，这些数据表明，白藜芦醇通过产生ROS抑制AKT/PKB途径导致细胞凋亡，同时通过上调DR5对TRAIL介导的凋亡启动DLBCL细胞。这些数据增加了白藜芦醇未来可能对DLBCL和其他AKT/PKB通路结构性激活的恶性肿瘤具有治疗作用的可能性。
We have recently shown that deregulation PI3-kinase/AKT survival pathway plays an important role in pathogenesis of diffuse large B cell lymphoma (DLBCL). In an attempt to identify newer therapeutic agents, we investigated the role of Resveratrol (trans-3,4′, 5-trihydroxystilbene), a naturally occurring polyphenolic compound on a panel of diffuse large B-cell lymphoma (DLBCL) cells in causing inhibition of cell viability and inducing apoptosis. We investigated the action of Resveratrol on DLBCL cells and found that Resveratrol inhibited cell viability and induced apoptosis by inhibition of constitutively activated AKT and its downstream targets via generation of reactive oxygen species (ROS). Simultaneously, Resveratrol treatment of DLBCL cell lines also caused ROS dependent upregulation of DR5; and interestingly, co-treatment of DLBCL with sub-toxic doses of TRAIL and Resveratrol synergistically induced apoptosis via utilizing DR5, on the other hand, gene silencing of DR5 abolished this effect. Altogether, these data suggest that Resveratrol acts as a suppressor of AKT/PKB pathway leading to apoptosis via generation of ROS and at the same time primes DLBCL cells via up-regulation of DR5 to TRAIL-mediated apoptosis. These data raise the possibility that Resveratrol may have a future therapeutic role in DLBCL and possibly other malignancies with constitutive activation of the AKT/PKB pathway.
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影响因子：
11.2
作者：
Hussain, Azhar R.;Al-Jomah, Naif A.;Uddin, Shahab
通讯作者：
Uddin, Shahab
影响因子：
5.7
作者：
Hussain, Azhar R.;Ahmed, Maqbool;Uddin, Shahab
通讯作者：
Uddin, Shahab
影响因子：
4.5
作者：
Galati, G;Sabzevari, O;O'Brien, PJ
通讯作者：
O'Brien, PJ
影响因子：
5.7
作者：
Bai, Yu;Mao, Qi-Qi;Xie, Li-Ping
通讯作者：
Xie, Li-Ping
影响因子：
8.5
作者：
Hussain, A. R.;Khan, A. S.;Uddin, S.
通讯作者：
Uddin, S.