CAS Key Laboratory of Chemistry of Northwestern Plant Resources and Key Laboratory for Natural Medicine of Gansu Province, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou 730000, China.
Laboratory of Anti-inflammation and Immunopharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Fitoterapia. 2021 Nov;155:105053. doi: 10.1016/j.fitote.2021.105053. Epub 2021 Oct 2.
It is commonly known that radiotherapy is still a key modality for treatment of cancer. Though this effect is desirable during radiotherapy, it leads to radiotoxicity on normal healthy cells. In the present research, we designed, synthesized and analyzed a series of nitronyl nitroxide radical (NITR) spin-labeled resveratrol (RES) derivatives. The cytotoxicity of the newly synthesized substances was tested on Jurkat T cells. The derivatives were studied as reactive oxygen species (ROS) scavenger to protect ionizing radiation of Jurkat T cells upon 6 Gy X-irradiation. The experimental results revealed that compound 2 and 3 could significantly alleviate the damage of Jurkat T cells, as evidenced by decreasing ROS production and restoring the cell apoptosis. Further mechanism investigations indicated that the radioprotective effects of the novel derivatives were largely associated with modulating the expression of apoptotic proteins including cIAP-1, cIAP-2, cytochrome c, caspase-3 and caspase-9. Based on the experimental result, we disclosed that the novel NITR spin-labeled RES derivatives exhibit the potential to be used as the novel radioprotective candidates to ameliorate the injury induced by ionizing radiation.
众所周知,放射疗法仍然是癌症治疗的一种关键方式。尽管这种效果在放射治疗中是理想的,但它会导致正常健康细胞的放射性毒性。在本研究中,我们设计、合成和分析了一系列硝酰氮自由基(NITR)自旋标记白藜芦醇(RES)衍生物。新合成物质的细胞毒性在 Jurkat T 细胞上进行了测试。研究了这些衍生物作为活性氧(ROS)清除剂,以保护 Jurkat T 细胞在 6Gy X 射线照射下的电离辐射。实验结果表明,化合物 2 和 3 能够显著减轻 Jurkat T 细胞的损伤,这表现在降低 ROS 的产生和恢复细胞凋亡。进一步的机制研究表明,新型衍生物的放射保护作用主要与调节凋亡蛋白的表达有关,包括 cIAP-1、cIAP-2、细胞色素 c、caspase-3 和 caspase-9。基于实验结果,我们揭示了新型 NITR 自旋标记 RES 衍生物具有作为新型放射保护剂的潜力,可改善电离辐射引起的损伤。