Department of Pathophysiology, School of Basic Medicine, Key Laboratory of Neurological Diseases, Ministry of Education, Hubei Provincial Key Laboratory of Neurological Diseases, Huazhong University of Science and Technology, Wuhan 430030, China.
Biochem Biophys Res Commun. 2013 Jul 19;437(1):87-93. doi: 10.1016/j.bbrc.2013.06.042. Epub 2013 Jun 22.
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 20μM 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 U87 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 U87 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 U87 cells. Our data first suggests that PL may have therapeutic potential for one of the most malignant and refractory tumors GBM.
胡椒碱（PL）是从荜茇中分离得到的一种天然生物碱，可能具有抗癌特性。它选择性地靶向并杀死癌细胞，而使正常细胞完好无损。在这里，我们报道 PL 通过积累活性氧（ROS）选择性地杀死多形性胶质母细胞瘤（GBM）细胞，从而激活 JNK 和 p38。20μM 的 PL 可在三种 GBM 细胞系（LN229、U87 和 8MG）中诱导严重的细胞死亡，但在培养物中的星形胶质细胞中则不会。PL 明显增加了 ROS，并降低了 LN229 和 U87 细胞中的谷胱甘肽水平。抗氧化剂 N-乙酰-L-半胱氨酸（NAC）完全逆转了 PL 诱导的 ROS 积累，并防止了 LN229 和 U87 细胞的死亡。在 LN229 和 U87 细胞中，PL 处理以剂量依赖性方式激活 JNK 和 p38，但不激活 Erk 和 Akt。这些激活可以通过 NAC 预处理来阻断。JNK 和 p38 的特异性抑制剂 SB203580 和 SP600125 分别显著阻断了 PL 在 LN229 和 U87 细胞中的细胞毒性作用。我们的数据首次表明，PL 可能对最恶性和难治性肿瘤 GBM 之一具有治疗潜力。
