Piperlongumine induces pancreatic cancer cell death by enhancing reactive oxygen species and DNA damage.
Piperlongumine induces pancreatic cancer cell death by enhancing reactive oxygen species and DNA damage.
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DOI：
10.1016/j.toxrep.2014.05.011
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发表时间：
2014
影响因子：
--
通讯作者：
Reindl, Katie M
中科院分区：
文献类型：
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作者：
Dhillon, Harsharan;Chikara, Shireen;Reindl, Katie M
胰腺癌是最致命的癌症之一，死亡率接近95%。胰腺癌对目前可用的疗法的不良反应和胰腺癌患者的极低存活率表明迫切需要替代治疗策略。使用活性氧（ROS）诱导剂已成为治疗各种癌症的创新和有效的策略。在这项研究中，我们研究了一种已知的ROS诱导剂，piperlongumine（PPLGM），一种在长辣椒中发现的生物活性剂，在细胞培养和动物模型中诱导胰腺癌细胞死亡的潜力。我们发现PPLGM通过升高ROS水平和引起DNA损伤来抑制胰腺癌细胞培养物的生长。PPLGM诱导的DNA损伤和胰腺癌细胞死亡通过用外源性抗氧化剂处理细胞而逆转。与体外研究相似，PPLGM在人胰腺癌异种移植小鼠模型中引起肿瘤生长减少。来自PPLGM处理的动物的肿瘤显示Ki-67降低和8-OHdG表达增加，表明PPLGM抑制肿瘤细胞增殖并增强氧化应激。总之，我们的结果表明，PPLGM是胰腺癌细胞体外和体内生长的有效抑制剂，并且它通过ROS介导的DNA损伤途径起作用。这些发现表明PPLGM具有用于治疗胰腺癌的潜力。
Pancreatic cancer is one of the most deadly cancers with a nearly 95% mortality rate. The poor response of pancreatic cancer to currently available therapies and the extremely low survival rate of pancreatic cancer patients point to a critical need for alternative therapeutic strategies. The use of reactive oxygen species (ROS)-inducing agents has emerged as an innovative and effective strategy to treat various cancers. In this study, we investigated the potential of a known ROS inducer, piperlongumine (PPLGM), a bioactive agent found in long peppers, to induce pancreatic cancer cell death in cell culture and animal models. We found that PPLGM inhibited the growth of pancreatic cancer cell cultures by elevating ROS levels and causing DNA damage. PPLGM-induced DNA damage and pancreatic cancer cell death was reversed by treating the cells with an exogenous antioxidant. Similar to the in vitro studies, PPLGM caused a reduction in tumor growth in a xenograft mouse model of human pancreatic cancer. Tumors from the PPLGM-treated animals showed decreased Ki-67 and increased 8-OHdG expression, suggesting PPLGM inhibited tumor cell proliferation and enhanced oxidative stress. Taken together, our results show that PPLGM is an effective inhibitor for in vitro and in vivo growth of pancreatic cancer cells, and that it works through a ROS-mediated DNA damage pathway. These findings suggest that PPLGM has the potential to be used for treatment of pancreatic cancer.