Curcumin suppresses constitutive activation of nuclear factor-κB and requires functional Bax to induce apoptosis in Burkitt's lymphoma cell lines
Curcumin suppresses constitutive activation of nuclear factor-κB and requires functional Bax to induce apoptosis in Burkitt's lymphoma cell lines
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DOI：
10.1158/1535-7163.mct-08-0541
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发表时间：
2008-10-01
影响因子：
5.7
通讯作者：
Uddin, Shahab
中科院分区：
文献类型：
--
作者：
Hussain, Azhar R.;Ahmed, Maqbool;Uddin, Shahab
我们提供的证据表明，姜黄素（一种从植物姜黄根茎中分离出来的天然化合物）可诱导几种表达 Bax 蛋白的伯基特淋巴瘤细胞系（AS283A、KK124 和 Pa682PB）凋亡，而对不表达 Bax 的细胞系（BML895 和 CA46）则没有影响。我们的数据表明，姜黄素处理会通过产生活性氧来下调核因子 kappa B (NF-kappa B) 的组成型激活，从而引起 Bax 蛋白的构象变化，从而导致线粒体膜电位丧失和细胞色素 c 释放到细胞质中。这会导致 caspase-9、caspase-3 和聚 (ADP)-核糖聚合酶裂解的激活，从而导致 caspase 依赖性细胞凋亡。此外，姜黄素治疗伯基特淋巴瘤细胞系也会导致 DR5 上调；然而，这种上调不会导致细胞凋亡。重要的是，姜黄素和 TRAIL 联合处理可诱导 Bax 缺陷细胞系凋亡。综上所述，我们的研究结果表明姜黄素能够诱导 Bax 阳性细胞系凋亡，而与 TRAIL 组合会导致 Bax 阴性细胞系凋亡。这些发现还提出了一种可能性，即在治疗方案中加入姜黄素可能为伯基特淋巴瘤的治疗提供一种新方法，并为未来的转化努力提供分子基础。 [摩尔癌症疗法 2008;7(10):3318-29]
We provide evidence that curcumin, a natural compound isolated from rhizomes of plant Curcuma longa, induces apoptosis in several Burkitt's lymphoma cell lines expressing Bax protein (AS283A, KK124, and Pa682PB), whereas it has no effects in cell lines with no Bax expression (BML895 and CA46). Our data show that curcumin treatment results in down-regulation of constitutive activation of nuclear factor-kappa B (NF-kappa B) via generation of reactive oxygen species where it causes conformational changes in Bax protein leading to loss of mitochondrial membrane potential and release of cytochrome c to the cytosol. This leads to activation of caspase-9, caspase-3, and poly(ADP)-ribose polymerase cleavage leading to caspase-dependent apoptosis. In addition, curcumin treatment of Burkitt's lymphoma cell lines also causes upregulation of DR5; however, this up-regulation does not result in apoptosis. Importantly, cotreatment with curcumin and TRAIL induces apoptosis in Bax-deficient cell lines. Taken together, our findings suggest that curcumin is able to induce apoptosis in Bax-positive cell lines, whereas combinations with TRAIL result in apoptosis in Bax-negative cell lines. These findings also raise the possibility that incorporation of curcumin in treatment regimens may provide a novel approach for the treatment of Burkitt's lymphomas and provide the molecular basis for such future translational efforts. [Mol Cancer Ther 2008;7(10):3318-29]