title: p38MAPK activation mediates tumor necrosis factor-α-induced apoptosis in glioma cells.
abstract: Gliomas are a type of heterogeneous primary central nervous system tumor, which arise from the glial cells; these types of tumor generally respond poorly to surgery, radiation and conventional chemotherapy. Tumor necrosis factor‑α (TNF‑α) has been suggested to produce an antitumor effect by binding to specific receptors on the tumor cell membrane to induce apoptosis. TNF‑α is known to activate a number of signaling pathways, including extracellular signal‑regulated protein kinase, c‑Jun N‑terminal kinase (JNK), p38 mitogen‑activated protein kinase (p38MAPK), nuclear factor‑κB and caspase cascades, depending on the cell type. However, the involvement of p38MAPK signaling in TNF‑α‑induced apoptosis in glioma cells remains unclear. In the current study, the role of p38MAPK in TNF‑α‑induced apoptosis in rat glioma C6 cells was investigated. TNF‑α was observed to induce cell apoptosis and the phosphorylation of p38MAPK in C6 cells. In addition, the inhibition of p38MAPK markedly reduced TNF‑α‑induced apoptosis, while JNK inhibition did not affect apoptosis. Furthermore, p38MAPK transfection altered the cell cycle of glioma cells and increased the rate of apoptosis. It also led to an increase in the level of soluble TNF‑α in the culture supernatant and membrane TNF receptor I levels in tumor cells. In conclusion, the results of the current study demonstrated that the activation of p38MAPK mediates TNF‑α‑induced apoptosis in glioma C6 cells, suggesting p38MAPK as a potential target for glioma therapy.
authors.affiliation: Department of Oncology, Wuhan General Hospital of Guangzhou Command, People's Liberation Army, Wuhan, Hubei 430070, P.R. China.
authors.forename: Bicheng
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Oncology, Wuhan General Hospital of Guangzhou Command, People's Liberation Army, Wuhan, Hubei 430070, P.R. China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Wu
authors.affiliation: Department of Oncology, Wuhan General Hospital of Guangzhou Command, People's Liberation Army, Wuhan, Hubei 430070, P.R. China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Oncology, Wuhan General Hospital of Guangzhou Command, People's Liberation Army, Wuhan, Hubei 430070, P.R. China.
authors.forename: Yafei
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Oncology, General Hospital, Jinan Command of People's Liberation Army, Jinan, Shandong 250031, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Oncology, Wuhan General Hospital of Guangzhou Command, People's Liberation Army, Wuhan, Hubei 430070, P.R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.affiliation: Department of Oncology, Wuhan General Hospital of Guangzhou Command, People's Liberation Army, Wuhan, Hubei 430070, P.R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Oncology, Wuhan General Hospital of Guangzhou Command, People's Liberation Army, Wuhan, Hubei 430070, P.R. China.
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Rao
authors.affiliation: Department of Oncology, Wuhan General Hospital of Guangzhou Command, People's Liberation Army, Wuhan, Hubei 430070, P.R. China.
authors.forename: Jianfei
authors.initials: J
authors.lastname: Gao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004789:Enzyme Activation; D015870:Gene Expression; D005910:Glioma / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism* / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases