title: Autophagy contributes to ING4-induced glioma cell death.
abstract: Previous studies suggest that ING4, a novel member of ING (inhibitor of growth) family, can inhibit brain tumor growth. However, whether autophagy is involved in ING4-induced cell death still remains unknown. In this study, we found that in addition to apoptosis, autophagy also contributed to cell death induced by ING4. Autophagy levels were elevated following the exposure to Ad-ING4, including enhanced fluorescence intensity of monodansylcadervarine (MDC), a specific in vivo marker for autophagic vacuoles, and increased expression levels of the LC3-II and Beclin-1, wheras the autophagic levels were attenuated following the pretreatment of 3-MA, the inhibitor of autophagy, which significantly decreased the Ad-ING4-induced cell death compared with caspase inhibitor zVAD. Furthermore, ING4 also induced mitochondrial dysfunction, such as mitophagy, collapse of mitochondrial membrane potential and the intracellular ROS, which indicated that mitochondria might be associated with the process of autophagic cell death of glioma cells. Finally, the relationship among Bax, Bcl-2, Beclin-1 and caspase family proteins levels were analyzed in glioma cells U251MG and LN229 infected with Ad-ING4 or Ad-lacZ. It is suggested that both autophagy and apoptosis could contribute to ING4-induced glioma cell death, and mitochondria might play an important role in this process. Our findings reveal novel aspects of the autophagy in glioma cells that underlie the cytotoxic action of ING4, possibly providing new insights in the development of combinatorial therapies for gliomas.
authors.affiliation: School of Medicine, Jiangsu University, Zhenjiang 212013, PR China. Electronic address: ahg5@ujs.edu.cn.
authors.forename: Aihua
authors.initials: A
authors.lastname: Gong
authors.affiliation: School of Pharmacy, Jiangsu University, Zhenjiang 212013, PR China.
authors.forename: Sisi
authors.initials: S
authors.lastname: Ye
authors.affiliation: School of Medicine, Jiangsu University, Zhenjiang 212013, PR China.
authors.forename: Ermeng
authors.initials: E
authors.lastname: Xiong
authors.affiliation: School of Pharmacy, Jiangsu University, Zhenjiang 212013, PR China.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Guo
authors.affiliation: School of Medicine, Jiangsu University, Zhenjiang 212013, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: School of Medicine, Jiangsu University, Zhenjiang 212013, PR China.
authors.forename: Wanxin
authors.initials: W
authors.lastname: Peng
authors.affiliation: School of Medicine, Jiangsu University, Zhenjiang 212013, PR China.
authors.forename: Genbao
authors.initials: G
authors.lastname: Shao
authors.affiliation: School of Medicine, Jiangsu University, Zhenjiang 212013, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Jin
authors.affiliation: School of Medicine, Jiangsu University, Zhenjiang 212013, PR China.
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: School of Medicine, Suzhou University, PR China.
authors.forename: Jicheng
authors.initials: J
authors.lastname: Yang
authors.affiliation: School of Pharmacy, Jiangsu University, Zhenjiang 212013, PR China. Electronic address: jinggao@ujs.edu.cn.
authors.forename: Jing
authors.initials: J
authors.lastname: Gao
mesh_terms: D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy; D000071186:Beclin-1; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D061945:Caspase Inhibitors / Q000494:pharmacology; D020169:Caspases / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D053078:Membrane Potential, Mitochondrial; D008565:Membrane Proteins / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D063306:Mitophagy; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D014617:Vacuoles / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D061945:Caspase Inhibitors; D018797:Cell Cycle Proteins; D018398:Homeodomain Proteins; C483230:ING4 protein, human; C477012:MAP1LC3A protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D025521:Tumor Suppressor Proteins; D051028:bcl-2-Associated X Protein; D020169:Caspases