Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Southwest Hospital, Third Military Medical University, Chongqing, China.
Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, China.
Lab Invest. 2017 Oct;97(10):1180-1187. doi: 10.1038/labinvest.2017.46. Epub 2017 May 15.
Nordihydroguaiaretic acid (NDGA) and its synthetic chiral analog dl-nordihydroguaiaretic acid (Nordy) show collective benefits in anti-tumor, and defending against viral and bacterial infections. Here, we synthetized a new derivative-NDGA-P21 based on NDGA structure. Regardless of the structural similarity, NDGA-P21 exhibited stronger capability in suppression of glioblastoma (GBM) cell growth as compared to Nordy. Mechanically, NDGA-P21 is able to arrest cell cycle of GBM cells in G0/G1 phase, and to block cell proliferation sequentially. It is important to note that NDGA-P21 is able to impair the stemness of glioma stem-like cells (GSLCs) via measurement of colony formation and sphere formation. Taken together, the novel NDGA-based compound NDGA-P21 exhibits potential therty -20 apeutic implications through inhibiting proliferation of glioma cells and self-renewal capability of GSLCs.
去甲二氢愈创木酸(NDGA)及其合成的手性对映体 dl-去甲二氢愈创木酸(Nordy)在抗肿瘤和预防病毒及细菌感染方面具有协同作用。在这里,我们基于 NDGA 结构合成了一种新的衍生物-NDGA-P21。尽管结构相似,但 NDGA-P21 抑制神经胶质瘤(GBM)细胞生长的能力比 Nordy 更强。从机制上讲,NDGA-P21 能够将 GBM 细胞的细胞周期阻滞在 G0/G1 期,并依次阻断细胞增殖。值得注意的是,NDGA-P21 通过集落形成和球体形成实验能够损害神经胶质瘤干细胞样细胞(GSLCs)的干性。总之,新型基于 NDGA 的化合物 NDGA-P21 通过抑制神经胶质瘤细胞的增殖和 GSLCs 的自我更新能力,显示出潜在的治疗意义。