荜茇酰胺对胶质瘤细胞的影响

Role of piperlongumine in glioma proliferation

目的探讨荜茇酰胺(piperlongumine,PL)对胶质瘤增殖以及侵袭的作用并阐明其作用机制。方法我们应用荜茇酰胺处理了两种不同的人脑胶质瘤细胞系,并用正常神经元细胞和胶质细胞作为对照。通过检测PL对于细胞ROS水平的改变以及细胞增殖信号通路的改变。随后检测了PL潜在的作用靶点PRDX4的活性改变。结果 PL能够显著增强两种人胶质瘤细胞的ROS水平以及抑制细胞增殖能力,但对正常神经元细胞则无明显影响。随后的检测中,我们发现PL刺激胶质瘤细胞后多种ROS相关的氧化反应调节因子都出现了上调,其中以PRDX家族中的PRDX4表达量上升最为明显。同时我们还发现,抑制ROS的作用之后,PL诱导胶质瘤细胞凋亡的能力出现了抑制。结论 PL能够通过提高PRDX4的表达从而介导胶质瘤细胞的凋亡,因此PL可能作为胶质瘤的潜在治疗药物。

Objective Piperlongumine,a natural plant product,kills multiple cancer types with littleeffect on normal cells.Piperlongumine raises intracellular levels of reactive oxygen species(ROS),a phenomenonthat may underlie the cancer-cell killing.Although these findings suggest that piperlongumine could be usefulfor treating cancers,the mechanism by which the drug selectively kills cancer cells remains unknown.MethodsWe treated multiple high-grade glioma(HGG)sphere cultures with piperlongumine and assessed its effects onROS and cell growth levels as well as changes in downstream signaling.We also examined the levels of putativepiperlongumine targets and their roles in HGG cell growth.Results Piperlongumine treatment increasedROS levels and preferentially killed HGG cells with little effect in normal brain cells.Piperlongumine reportedlyincreases ROS levels after interactions with several redox regulators.Furthermore,piperlongumine treatment inHGG cells,but not in normal NSCs,increased oxidative inactivation of peroxiredoxin4(PRDX4),an ROS-reducingenzyme that is overexpressed in HGGs.Moreover,piperlongumine’s effects was blocked after the inhibitionof ROS overexpression in glioma cells.Conclusion Our results reveal that the mechanism by which piperlonguminepreferentially kills HGG cells involves PRDX4inactivation.Therefore,piperlongumine treatment could beconsidered as a novel therapeutic option for HGG treatment.