DR5 related autophagy can promote apoptosis in gliomas after irradiation

• Published in: Biochemical and biophysical research communications Vol. 522; no. 4; pp. 910 - 916
• Main Authors: Zhang, Peng, Wang, Hailong, Chen, Yu, Lodhi, Adil Farooq, Sun, Chunli, Sun, Feiyi, Yan, Liben, Deng, Yulin, Ma, Hong
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 19.02.2020
• Subjects: Apoptosis; Autophagy; DR5; Glioma; Irradiation tolerance; Glioma; Irradiation tolerance; Autophagy; DR5; Apoptosis
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2019.11.161

As a cancer treatment strategy, irradiation therapy is widely used that can cause DNA breakage and increase free radicals, which leads to different types of cell death. Among them, apoptosis and autophagy are the most important and the most studied cell death processes. Although the exploration of the relationship between apoptosis and autophagy has been a major area of focus, still the molecular mechanisms of autophagy on apoptosis remain unclear. Here, we have revealed that apoptosis was enhanced by the death receptor 5 (DR5) pathway, and the effect of autophagy on apoptosis was promoted by DR5 interacting with LC3B as well as Caspase8 in gliomas after irradiation. Interestingly, we observed that the addition of four different autophagy inducers, rapamycin (RAP), CCI779, ABT737 and temozolomide (TMZ), induced the differences of DR5 expression and cell apoptosis after irradiation. Unlike RAP and CCI779, ABT737 and TMZ were able to increase DR5 expression and further induce cell death. Therefore, we have concluded that DR5 plays a novel and indispensable role in promoting cell apoptosis under irradiation and suggest a potential therapeutic approach for glioblastoma treatment. •Irradiation can increase the levels of apoptosis and autophagy in gliomas.•DR5 promotes cell death by interacting with LC3B and Caspase8 after irradiation.•DR5 can be used as a marker of cell sensitivity.•The formation of autophagic lysosomes inhibits apoptosis.