WZY-321, a novel evodiamine analog, inhibits glioma cell growth in an autophagy-associated manner

Abstract

Glioblastoma is one of the most aggressive types of brain tumor. The median survival rate of patients with glioblastoma (World Health Organization grade IV) is <15 months. Therefore, there is an urgent requirement for the development of novel and efficient therapeutic agents against glioma. In previous studies, WZY-321 (10-hydroxy-1-methyl-8,13b-dihydr o-5H,7H-benzo[e]benzofuro[2',3':3,4]pyrido[2,1-b][1,3]oxazin- 5-one), a novel evodiamine (Evo) analog, was reported to exhibit enhanced pharmacological properties and improved cytotoxicity against a number of human cancer cell lines compared with Evo. In the current study, the anti-proliferative effect of WZY-321 on SHG-44 and SWO-38 glioma cells was further studied, and its mechanism of action investigated. The results indicated that WZY-321 inhibited the proliferation of SHG-44 cells in a dose- and time-dependent manner by enhancing cellular apoptosis and inducing cell cycle arrest at the G2-M phase. Treatment of glioma cells with WZY-321 concomitantly increased the expression levels of microtubule associated protein 1 light chain 3α and Beclin1, indicating enhanced autophagy. Overall, the results of the present study revealed the anti-proliferative potential of WZY-321 in glioma cells, thus providing a possible autophagy-based therapeutic strategy for the treatment of glioblastoma.