Plumbagin Triggers ER Stress-Mediated Apoptosis in Prostate Cancer Cells via Induction of ROS
Plumbagin Triggers ER Stress-Mediated Apoptosis in Prostate Cancer Cells via Induction of ROS
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DOI：
10.1159/000486773
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发表时间：
2018-01-01
影响因子：
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通讯作者：
Chen, Wei
中科院分区：
文献类型：
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作者：
Huang, Hang;Xie, Hui;Chen, Wei
背景/目的：前列腺癌（PCa）是世界范围内第二大最常见的男性癌症。目前可用于激素难治性PCa的治疗方法效果甚微。白丹素（PLB）是一种从传统民间药材白丹中分离出来的天然萘醌，具有选择性杀伤肿瘤细胞的作用。然而，PLB在癌细胞中的抗肿瘤机制尚未完全确定。方法：采用MTT法观察PLB对肿瘤细胞活力的影响。流式细胞术检测细胞凋亡和活性氧（ROS）的产生。western blotting检测蛋白表达。采用裸鼠肿瘤异种移植模型测定体内抗肿瘤作用。结果：在本研究中，我们发现PLB可以抑制DU145和PC-3细胞的生长，诱导细胞凋亡。此外，通过增加细胞内ROS水平，PLB在PCa细胞中诱导了致命的内质网应激反应。重要的是，阻断ROS的产生可显著逆转plb诱导的内质网应激激活和细胞凋亡。在体内，我们发现PLB抑制PCa异种移植物的生长而没有表现出毒性。用PLB处理携带人PCa异种移植物的小鼠也与内质网应激激活的诱导有关。结论：通过PLB诱导内质网应激揭示了PLB生物活性的未知机制，为PLB在激素难治性PCa治疗中的作用提供了深入的见解。(C) 2018作者：s . Karger AG，巴塞尔出版
Background/Aims: Prostate cancer (PCa) is the second most frequently diagnosed cancer in men worldwide. Currently available therapies for hormone-refractory PCa are only marginally effective. Plumbagin (PLB), a natural naphthoquinone isolated from the traditional folk medicine Plumbago zeylanica, is known to selectively kill tumor cells. Nevertheless, antitumor mechanisms initiated by PLB in cancer cells have not been fully defined. Methods: MTT assay was used to evaluate the effect of PLB on the viability of cancer cells. Cell apoptosis and reactive oxygen species (ROS) production were determined by flow cytometry. Protein expression was detected by western blotting. In vivo anti-tumor effect was measured by using tumor xenograft model in nude mice. Results: In the present study, we found that PLB decreases cancer cell growth and induces apoptosis in DU145 and PC-3 cells. In addition, by increasing intracellular ROS levels, PLB induced a lethal endoplasmic reticulum stress response in PCa cells. Importantly, blockage of ROS production significantly reversed PLB-induced ER stress activation and cell apoptosis. In vivo, we found that PLB inhibits the growth of PCa xenografts without exhibiting toxicity. Treatment of mice bearing human PCa xenografts with PLB was also associated with induction of ER stress activation. Conclusion: Inducing ER stress by PLB thus discloses a previously unrecognized mechanism underlying the biological activity of PLB and provides an in-depth insight into the action of PLB in the treatment of hormone refractory PCa. (C) 2018 The Author(s) Published by S. Karger AG, Basel