1′-Acetoxychavicol acetate induces apoptosis of myeloma cells via induction of TRAIL
1′-Acetoxychavicol acetate induces apoptosis of myeloma cells via induction of TRAIL
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DOI：
10.1016/j.bbrc.2005.10.153
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发表时间：
2005-12-30
影响因子：
3.1
通讯作者：
Kizaki, M
中科院分区：
文献类型：
--
作者：
Ito, K;Nakazato, T;Kizaki, M
传统泰国调味品的一种成分，1 '-乙酰氧基胡椒酚乙酸酯（ACA），是一种天然化合物，它是从民族药用植物大高良姜（菊科）的根茎中获得的。我们的前期研究表明ACA通过激活caspase-8、灭活NF-κ B B和下调抗凋亡蛋白诱导多发性骨髓瘤细胞凋亡，从而显著抑制多发性骨髓瘤细胞的生长。随后，我们研究了ACA的详细凋亡途径，并进一步证明ACA上调TNF相关的凋亡诱导配体/Apo 2配体（TRAIL/Apo 2L）和TRAIL受体死亡受体5（DR 5）的表达。此外，TRAIL/R-Fc嵌合体中和ACA诱导的细胞凋亡。这些结果表明，TRAIL的死亡信号参与了ACA诱导的骨髓瘤细胞凋亡，为ACA诱导TRAIL/Apo 2L的表达提供了理论依据，并有望成为治疗多发性骨髓瘤的新药物。(c)2005年爱思唯尔公司All rights reserved.
A component of a traditional Thai condiment, 1'-acetoxychavicol acetate (ACA), is a natural compound, and it is obtained from rhizomes of the ethno-medicinal plant Languas galanga (Zingiberaceae). Our previous studies showed that ACA dramatically inhibited cellular growth of multiple myeloma cells in vivo and in vitro through the induction of apoptosis in association with the activation of caspase-8, inactivation of NF-kappa B, and down-regulation of anti-apoptotic proteins. Subsequently, we investigated the detailed apoptotic pathway of ACA and further demonstrated that ACA up-regulates the expression of both TNF-related apoptosis-inducing ligand/Apo2 ligand (TRAIL/Apo2L) and TRAIL receptor death receptor 5 (DR5). In addition, TRAIL/R-Fc chimera neutralizes the ACA-induced apoptosis. These results suggest that the death signaling of TRAIL is involved in the ACA-induced apoptosis of myeloma cells, and provide a rationale for the induction of TRAIL/Apo2L by ACA, which could potentially be used as a novel therapeutic agent in patients with multiple myeloma. (c) 2005 Elsevier Inc. All rights reserved.