title: IL-24 Induces Apoptosis via Upregulation of RNA-Activated Protein Kinase and Enhances Temozolomide-Induced Apoptosis in Glioma Cells.
abstract: Human interleukin-24 (IL-24) has been found recently to play a tumor-suppressor role in a variety of tumors, including gliomas. However, the exact mechanism of glioma tumor suppression by IL-24 remains unclear. We collected by surgery 30 gliomas at different grades and evaluated IL-24 and double-stranded RNA-activated protein kinase (PKR) expression using fluorescence quantitative real-time PCR and immunohistochemical techniques. Two human glioma cell lines, U87 and U251, were transfected with Ad5F35-IL24 via recombinant adenovirus-mediated gene transfer and apoptosis, as well as PKR and eIF-2α expression analyzed. The results showed that IL-24 and PKR expression decreased with increasing tumor grade. Compared with cells of the control groups, Ad5F35-IL24-infected U87 and U251 cells exhibited a significantly increased apoptosis and elevated PKR, eIF-2α, p-PKR, and p-eIF-2α levels, while the expression of Bcl-2 was decreased. Finally, IL-24 also sensitized apoptosis of glioma cells to temozolomide (TMZ). This study indicates that IL-24 upregulates expression and activation of PKR, further increasing expression and activation of eIF-2α, and decreasing Bcl-2 to promote apoptosis. IL-24 also increases chemosensitivity of glioma cells to TMZ.
authors.affiliation: Third Department of Neurosurgery, Cangzhou Central Hospital, Cangzhou, China.
authors.forename: Chang-Wei
authors.initials: CW
authors.lastname: Hu
authors.forename: Gang-Feng
authors.initials: GF
authors.lastname: Yin
authors.forename: Xi-Rui
authors.initials: XR
authors.lastname: Wang
authors.forename: Bao-Wen
authors.initials: BW
authors.lastname: Ren
authors.forename: Wen-Gao
authors.initials: WG
authors.lastname: Zhang
authors.forename: Qing-Ling
authors.initials: QL
authors.lastname: Bai
authors.forename: Yan-Ming
authors.initials: YM
authors.lastname: Lv
authors.forename: Wen-Ling
authors.initials: WL
authors.lastname: Li
authors.forename: Wen-Qing
authors.initials: WQ
authors.lastname: Zhao
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D045744:Cell Line, Tumor; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000494:pharmacology; D005910:Glioma / Q000188:drug therapy / Q000473:pathology*; D006801:Humans; D007378:Interleukins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D011994:Recombinant Proteins / Q000235:genetics; D000077204:Temozolomide; D014162:Transfection; D015854:Up-Regulation; D019892:eIF-2 Kinase / Q000096:biosynthesis*; D000099180:Interleukin-24
chemical_list: D003606:Dacarbazine; D007378:Interleukins; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins; D000077204:Temozolomide; D019892:eIF-2 Kinase; D000099180:Interleukin-24