Piperlongumine selectively kills glioblastoma multiforme cells via reactive oxygen species accumulation dependent JNK and p38 activation
Piperlongumine selectively kills glioblastoma multiforme cells via reactive oxygen species accumulation dependent JNK and p38 activation
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Piperlongumine 通过活性氧积累依赖的 JNK 和 p38 激活选择性杀死多形性胶质母细胞瘤细胞
DOI：
10.1016/j.bbrc.2013.06.042
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发表时间：
2013-07-19
影响因子：
3.1
通讯作者：
Chen, Xiao Qian
中科院分区：
文献类型：
--
作者：
Liu, Ju Mei;Pan, Feng;Chen, Xiao Qian
胡椒碱是一种从辣椒中分离出来的天然生物碱，具有抗癌作用。它选择性地靶向并杀死癌细胞，但不破坏正常细胞。在这里，我们报道了PL通过积累活性氧（ROS）激活JNK和p38来选择性地杀死多形性胶质母细胞瘤（GBM）细胞。20 μ M的PL可诱导3株GBM细胞系（LN229、U87和8MG）严重细胞死亡，但对培养的星形胶质细胞无诱导作用。PL显著提高了LN229和1387细胞的ROS水平，降低了谷胱甘肽水平。抗氧化剂n -乙酰- l-半胱氨酸（NAC）完全逆转pl诱导的ROS积累，防止LN229和U87细胞死亡。在LN229和1387细胞中，pl处理激活了JNK和p38，但没有激活Erk和Akt，且呈剂量依赖性。NAC预处理可以阻断这些活化。JNK和p38特异性抑制剂SB203580和SP600125在LN229和1387细胞中显著阻断了PL的细胞毒作用。我们的数据首先表明，PL可能对最恶性和难治性肿瘤GBM之一具有治疗潜力。(c) 2013爱思唯尔公司版权所有。
Piperlongumine (PL), a natural alkaloid isolated from the long pepper, may have anti-cancer properties. It selectively targets and kills cancer cells but leaves normal cells intact. Here, we reported that PL selectively killed glioblastoma multiforme (GBM) cells via accumulating reactive oxygen species (ROS) to activate JNK and p38. PL at 20 mu M could induce severe cell death in three GBM cell lines (LN229, U87 and 8MG) but not astrocytes in cultures. PL elevated ROS prominently and reduced glutathione levels in LN229 and 1387 cells. Antioxidant N-acetyl-L-cysteine (NAC) completely reversed PL-induced ROS accumulation and prevented cell death in LN229 and U87 cells. In LN229 and 1387 cells, PL-treatment activated JNK and p38 but not Erk and Akt, in a dosage-dependent manner. These activations could be blocked by NAC pre-treatment. JNK and p38 specific inhibitors, SB203580 and SP600125 respectively, significantly blocked the cytotoxic effects of PL in LN229 and 1387 cells. Our data first suggests that PL may have therapeutic potential for one of the most malignant and refractory tumors GBM. (c) 2013 Elsevier Inc. All rights reserved.