AbstractZerumbone, a natural monocy

Abstract
Zerumbone, a natural monocyclic sesquiterpene, is the main component of the tropical plant Zingiber zerumbet Smith. Zerumbone induced antiproliferative and apoptotic effects against PC-3 and DU-145, two human hormone-refractory prostate cancer (HRPC) cell lines. Zerumbone inhibited microtubule assembly and induced an increase of MPM-2 expression (specific recognition of mitotic proteins). It also caused an increase of phosphorylation of Bcl-2 and Bcl-xL, two key events in tubulin-binding effect, indicating tubulin-binding capability and mitotic arrest to zerumbone action. Furthermore, zerumbone induced several cellular effects distinct from tubulin-binding properties. First, zerumbone significantly increased, while paclitaxel (as a tubulin-binding control) decreased, Mcl-1 protein expression. Second, paclitaxel but not zerumbone induced Cdk1 activity. Third, zerumbone other than paclitaxel induced Cdc25C downregulation. The data suggest that, in addition to targeting tubulin/microtubule, zerumbone may act on other targets for signaling transduction. Zerumbone induced mitochondrial damage and endoplasmic reticulum (ER) stress as evidenced by the loss of mitochondrial membrane potential and upregulation of GRP-78 and CHOP/GADD153 expression. Zerumbone induced an increase of intracellular Ca(2+) levels, a crosstalk marker between ER stress and mitochondrial insult, associated with the formation of active calpain I fragment. It induced apoptosis through a caspase-dependent way and caused autophagy as evidenced by dramatic LC3-II formation. In summary, the data suggest that zerumbone is a multiple targeting compound that inhibits tubulin assembly and induces a crosstalk between ER stress and mitochondrial insult, leading to apoptosis and autophagy in HRPCs.

結果 (中文) 1:

摘要Zerumbone, a natural monocyclic sesquiterpene, is the main component of the tropical plant Zingiber zerumbet Smith. Zerumbone induced antiproliferative and apoptotic effects against PC-3 and DU-145, two human hormone-refractory prostate cancer (HRPC) cell lines. Zerumbone inhibited microtubule assembly and induced an increase of MPM-2 expression (specific recognition of mitotic proteins). It also caused an increase of phosphorylation of Bcl-2 and Bcl-xL, two key events in tubulin-binding effect, indicating tubulin-binding capability and mitotic arrest to zerumbone action. Furthermore, zerumbone induced several cellular effects distinct from tubulin-binding properties. First, zerumbone significantly increased, while paclitaxel (as a tubulin-binding control) decreased, Mcl-1 protein expression. Second, paclitaxel but not zerumbone induced Cdk1 activity. Third, zerumbone other than paclitaxel induced Cdc25C downregulation. The data suggest that, in addition to targeting tubulin/microtubule, zerumbone may act on other targets for signaling transduction. Zerumbone induced mitochondrial damage and endoplasmic reticulum (ER) stress as evidenced by the loss of mitochondrial membrane potential and upregulation of GRP-78 and CHOP/GADD153 expression. Zerumbone induced an increase of intracellular Ca(2+) levels, a crosstalk marker between ER stress and mitochondrial insult, associated with the formation of active calpain I fragment. It induced apoptosis through a caspase-dependent way and caused autophagy as evidenced by dramatic LC3-II formation. In summary, the data suggest that zerumbone is a multiple targeting compound that inhibits tubulin assembly and induces a crosstalk between ER stress and mitochondrial insult, leading to apoptosis and autophagy in HRPCs.

結果 (中文) 2:

抽象
球姜酮，天然的单环倍半萜烯，是热带植物红球姜史密斯的主要成分。球姜酮诱导抗增殖和抗PC-3和DU-145，两种人激素难治性前列腺癌（HRPC）细胞系的凋亡抑制作用。球姜酮抑制微管组装和诱导MPM-2表达的增加（特异性识别的有丝分裂的蛋白质）。它也造成的Bcl-2和Bcl-xL的磷酸化的增加，在微管蛋白结合的影响的两个关键事件，指示球姜酮动作微管蛋白结合能力和有丝分裂停滞。此外，球姜酮诱导的从微管蛋白结合性质不同的几个细胞的效果。第一，球姜酮显著增加，而紫杉醇（如微管蛋白结合对照）降低，Mcl-1的蛋白质表达。第二，紫杉醇但不能诱导球姜酮CDK1活动。三，比球姜酮诱导紫杉醇下调CDC25C等。数据表明，除了靶向微管蛋白/微管，球姜酮可能对其他目标行事信号转导。球姜酮诱导的线粒体损伤和如由线粒体膜电位和GRP-78与CHOP / GADD153表达上调的损失质网（ER）应力。球姜酮诱导（2+）水平的增加细胞内Ca，ER应激和线粒体损伤之间的串扰的标记，用活性钙蛋白酶I片段的形成有关。它诱导细胞凋亡通过caspase依赖的方式引起的自噬戏剧性LC3-II的形成就是明证。综上所述，

結果 (中文) 3:

摘要结果发现zerumbone，天然的单环倍半萜，是热带植物红球姜史密斯的主要成分。对前列腺癌PC-3和DU-145 ZER诱导的生长抑制及诱导凋亡的作用，两人激素难治性前列腺癌细胞株（HRPC）。结果发现zerumbone抑制微管的组装和诱导期表达增加（有丝分裂蛋白的特异性识别）。这也引起增加磷酸化Bcl-2、Bcl-xl在微管蛋白结合作用的两个关键事件，表明微管蛋白的结合能力和有丝分裂逮捕zerumbone行动。此外，Zerumbone所引起的几个细胞的影响不同的微管蛋白结合特性。首先，Zerumbone显著增加，而紫杉醇（如微管蛋白结合控制）降低，Mcl-1蛋白表达。第二，紫杉醇而不花姜酮诱导CDK1活性。第三，Zerumbone比紫杉醇诱导的蛋白表达下调。数据显示，除了针对微管，Zerumbone可能作用于信号转导等目标。花姜酮诱导的线粒体损伤及内质网（ER）应力证明了线粒体膜电位下降，上调GRP-78和CHOP/GADD153表达。花姜酮诱导的细胞内增加的Ca（2 +）水平，内质网应激及线粒体损伤之间的串扰的标记，具有主动Calpain I片段的形成有关。它诱导的细胞凋亡通过caspase依赖的方式，通过戏剧性的LC3-II证明形成引起的自噬。总之，这些数据表明，Zerumbone是一个多目标化合物抑制微管蛋白装配和诱导内质网应激及线粒体损伤之间的串扰，导致HRPCs凋亡和自噬。