Allaman-Pillet Nathalie, Schorderet Daniel F
Institute for Research in Ophthalmology, Sion, Switzerland.
University of Lausanne, Faculty of Biology and Medicine, Lausanne, Switzerland.
Oncotarget. 2021 Apr 27;12(9):907-916. doi: 10.18632/oncotarget.27947.
Retinoblastoma is the most common pediatric intraocular malignant tumor. While retinoblastoma initiation is triggered by the inactivation of both alleles of the retinoblastoma tumor suppressor gene () in the developing retina, tumor progression requires additional epigenetic changes, retinoblastoma genomes being quite stable. Although the management of RB has recently improved, new therapeutic agents are necessary to improve the treatment of advanced forms of retinoblastoma. In this report, we analyzed the pro-death effect of piperlongumine (PL), a natural compound isolated from Piper longum L., on two human retinoblastoma cell lines, WERI-Rb and Y79. The effects of PL on cell proliferation, cell death and cell cycle were investigated. PL effectively inhibited cell growth, impacted the cell cycle by decreasing the level of cyclins and CDK1 and increasing CDKN1A and triggered a caspase-3 independant cell death process in which reactive oxygen species (ROS) production is a major player. Indeed, PL toxicity in retinoblastoma cell lines was inhibited by a ROS scavenger N-acetyl-l-cysteine (NAC) treatment. These findings suggest that PL reduces tumor growth and induces cell death by regulating the cell cycle.
视网膜母细胞瘤是最常见的儿童眼内恶性肿瘤。虽然视网膜母细胞瘤的发生是由发育中的视网膜中视网膜母细胞瘤肿瘤抑制基因（）的两个等位基因失活触发的，但肿瘤进展需要额外的表观遗传变化，视网膜母细胞瘤基因组相当稳定。尽管视网膜母细胞瘤的治疗最近有所改善，但仍需要新的治疗药物来改善晚期视网膜母细胞瘤的治疗。在本报告中，我们分析了从荜茇中分离出的天然化合物胡椒碱（PL）对两种人视网膜母细胞瘤细胞系WERI-Rb和Y79的促死亡作用。研究了PL对细胞增殖、细胞死亡和细胞周期的影响。PL有效抑制细胞生长，通过降低细胞周期蛋白和CDK1水平以及增加CDKN1A来影响细胞周期，并触发了一个半胱天冬酶-3非依赖性细胞死亡过程，其中活性氧（ROS）的产生起主要作用。事实上，视网膜母细胞瘤细胞系中的PL毒性通过ROS清除剂N-乙酰-L-半胱氨酸（NAC）处理而受到抑制。这些发现表明，PL通过调节细胞周期来减少肿瘤生长并诱导细胞死亡。
