Plumbagin, a medicinal plant-derived naphthoquinone, is a novel inhibitor of the growth and invasion of hormone-refractory prostate cancer.
Plumbagin, a medicinal plant-derived naphthoquinone, is a novel inhibitor of the growth and invasion of hormone-refractory prostate cancer.
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DOI：
10.1158/0008-5472.can-08-2494
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发表时间：
2008-11-01
期刊：
影响因子：
11.2
通讯作者：
Verma, Ajit K.
中科院分区：
文献类型：
--
作者：
Aziz, Moammir H.;Dreckschmidt, Nancy E.;Verma, Ajit K.
前列腺癌（PCa）是男性癌症相关死亡的第二大原因。激素难治性侵袭性PCa是终末期，占PCa患者死亡的大多数。我们在这里提出，白花丹素（PL），醌类成分分离自药用植物白花丹的根，可能是一个潜在的新的代理人在控制激素难治性前列腺癌。具体的观察结果是，PL抑制PCa细胞的侵袭和选择性诱导PCa细胞的凋亡，但不是在永生化的非致瘤性前列腺上皮RWPE-1细胞。此外，在异位植入激素难治性DU 145 PCa细胞后3天开始腹膜内施用PL（2 mg/kg体重），使肿瘤生长延迟3周，并使肿瘤重量和体积均减少90%。在PL处理的小鼠中，停止PL处理长达4周不会导致肿瘤生长的进展。低至5 μM的PL可抑制培养的PCa细胞和DU 145异种移植物中的以下表达：1）PKCε、PI 3 K、pAKT、pJAK-2和pStat 3; 2）转录因子AP-1、NF κ B和Stat 3的DNA结合活性; 3）Bcl-xL、cdc 25 A和考克斯-2的表达。结果首次表明，使用体外和体内临床前模型，PL抑制PCa的生长和侵袭。PL抑制多个分子靶点，包括PKCε，PCa侵袭性的预测生物标志物。PL可能是治疗激素难治性前列腺癌的一种新药。
Prostate cancer (PCa) is the second leading cause of cancer-related deaths in men. Hormone refractory invasive PCa is the end stage and accounts for the majority of PCa patient deaths. We present here that plumbagin (PL), a quinoid constituent isolated from the root of the medicinal plant Plumbago zeylanica L, may be a potential novel agent in the control of hormone refractory PCa. Specific observations are the findings that PL inhibited PCa cell invasion and selectively induced apoptosis in PCa cells but not in immortalized non-tumorigenic prostate epithelial RWPE-1 cells. Also, intraperitoneal administration of PL (2mg/kg body weight), beginning 3 days after ectopic implantation of hormone refractory DU145 PCa cells, delayed tumor growth by 3 weeks and reduced both tumor weight and volume by 90%. Discontinuation of PL treatment in PL- treated mice, for as long as 4 weeks did not result in progression of tumor growth. PL, at concentrations as low as 5 μM, inhibited both in cultured PCa cells and DU145 xenografts the expression of: 1) PKCε, PI3K, pAKT, pJAK-2 and pStat3; 2) the DNA-binding activity of transcription factors AP-1, NFkB, and Stat3 and 3) Bcl-xL, cdc25A and COX-2 expression. The results indicate for the first time, using both in vitro and in vivo preclinical models, that PL inhibits the growth and invasion of PCa. PL inhibits multiple molecular targets including PKCε, a predictive biomarker of PCa aggressiveness. PL may be a novel agent for therapy of hormone refractory PCa.