Uddin Shahab, Hussain Azhar R, Manogaran Pulicat S, Al-Hussein Khaled, Platanias Leonidas C, Gutierrez Marina I, Bhatia Kishor G
King Fahad National Center for Children's Cancer and Research, Riyadh, Saudi Arabia.
Oncogene. 2005 Oct 27;24(47):7022-30. doi: 10.1038/sj.onc.1208864.
The mechanisms that regulate induction of the antiapoptotic state and mitogenic signals in primary effusion lymphoma (PEL) are not well known. In efforts to identify novel approaches to block the proliferation of PEL cells, we found that curcumin (diferuloylmethane), a natural compound isolated from the plant Curcuma Ionga, inhibits cell proliferation and induces apoptosis in a dose dependent manner in several PEL cell lines. Such effects of curcumin appear to result from suppression of the constitutively active STAT3 through inhibition of Janus kinase 1 (JAK1). Our data also demonstrate that curcumin induces loss of mitochondrial membrane potential with subsequent release of cytochrome c and activation of caspase-3, followed by polyadenosin-5'-diphosphate-ribose polymerase (PARP) cleavage. Altogether, our findings suggest a novel function for curcumin, acting as a suppressor of JAK-1 and STAT3 activation in PEL cells, leading to inhibition of proliferation and induction of caspase-dependent apoptosis. Therefore, curcumin may have a future therapeutic role in PEL and possibly other malignancies with constitutive activation of STAT3.
调节原发性渗出性淋巴瘤（PEL）中抗凋亡状态和促有丝分裂信号诱导的机制尚不清楚。为了寻找阻断PEL细胞增殖的新方法，我们发现姜黄素（二阿魏酰甲烷），一种从植物姜黄中分离出的天然化合物，在几种PEL细胞系中以剂量依赖的方式抑制细胞增殖并诱导凋亡。姜黄素的这种作用似乎是通过抑制Janus激酶1（JAK1）来抑制组成型活化的信号转导和转录激活因子3（STAT3）而产生的。我们的数据还表明，姜黄素诱导线粒体膜电位丧失，随后细胞色素c释放和半胱天冬酶-3激活，接着是聚腺苷酸-5'-二磷酸-核糖聚合酶（PARP）裂解。总之，我们的研究结果表明姜黄素具有一种新功能，作为PEL细胞中JAK-1和STAT3激活的抑制剂，导致增殖抑制和半胱天冬酶依赖性凋亡的诱导。因此，姜黄素可能在PEL以及可能其他具有STAT3组成型激活的恶性肿瘤中具有未来的治疗作用。
