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

Sun,Guan; Zhang,Chuang; Song,Hongmao; Guo,Jun; Li,Min; Cao,Ying

doi:10.3892/ol.2018.9847

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

Authors:
- Guan Sun
- Chuang Zhang
- Hongmao Song
- Jun Guo
- Min Li
- Ying Cao
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Affiliations: Department of Neurosurgery, The First People's Hospital of Yancheng, Fourth Affiliated Hospital of Nantong University, Yancheng, Jiangsu 224001, P.R. China, Department of Medical Oncology, The Eighty‑First Hospital of People's Liberation Army, Nanjing, Jiangsu 210002, P.R. China, Department of Ear‑Nose‑Throat, Huai'an Second People's Hospital, The Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an, Jiangsu 223002, P.R. China, Department of Neurosurgery, Jiangning Hospital Affiliated with Nanjing Medical University, Nanjing, Jiangsu 211100, P.R. China
Published online on: December 18, 2018 https://doi.org/10.3892/ol.2018.9847
Pages: 2465-2472

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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‑dihydro‑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.

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