Mechanisms of Resistance of Human Glioma Cells to Apo2 Ligand/TNF-Related Apoptosis-Inducing Ligand

Rieger, Johannes; Frank, Brigitte; Weller, Michael; Wick, Wolfgang
July 2007
Cellular Physiology & Biochemistry (Karger AG);2007, Vol. 20 Issue 1-4, p023
Academic Journal
Background: Many tumor cells are resistant to Apo2L/TRAIL-induced apoptosis in the absence of inhibitors of protein synthesis. Apo2L/TRAIL, in addition to induction of apoptosis, may therefore also activate survival pathways. Methods: Here we investigated whether such survival pathways mediate resistance to Apo2L.0-induced apoptosis in human glioma cells. Results: Apo2L.0 induced the phosphorylation of ERK1/2, but not of Akt. This effect was unaffected by caspase inhibition. Inhibitors of protein synthesis, PI3 kinase, ERK kinase, NF-κB or casein kinase 2 sensitized for Apo2L.0-induced apoptosis to a different extent in a panel of human malignant glioma cell lines. However, none of the sensitizers overcame resistance mediated by ectopic expression of the viral caspase 8 inhibitor, crm-A. Primary glioma cultures were almost completely resistant to Apo2L.0-induced cell death even in the presence of the inhibitors. Caspase-8 was expressed in these cells whereas only weak expression of DR5 was detected. Transient expression of DR5 conferred sensitivity to Apo2L.0. Conclusion: These data challenge the view that specific cell lines harbour specific mechanisms of resistance to Apo2L/TRAIL. Weak expression of DR5 in primary glioma might limit the therapeutic application of Apo2L/TRAIL in human glioblastoma patients. Copyright © 2007 S. Karger AG, Basel


Related Articles

  • Pregnenolone, a cholesterol metabolite, induces glioma cell apoptosis via activating extrinsic and intrinsic apoptotic pathways. XIAO XIAO; LIJUN CHEN; YING OUYANG; WENBO ZHU; PENGXIN QIU; XINWEN SU; YUNLING DOU; LIPENG TANG; MIN YAN; HAIPENG ZHANG; XIAOXIAO YANG; DONG XU; GUANGMEI YAN // Oncology Letters;2014, Vol. 8 Issue 2, p645 

    Gliomas are one of the most common types of malignant tumors worldwide, however, an effective therapeutic strategy not yet been fully determined. The present study aimed to investigate the anti-glioma activity and underlying mechanisms of pregnenolone, which originates from cholesterol and is...

  • Resistance Against Ricin-Induced Apoptosis in a Brefeldin A-Resistant Mutant Cell Line (BER-40) of Vero Cells. Tamura, Tadashi; Oda, Tatsuya; Muramatsu, Tsuyoshi // Journal of Biochemistry;2002, Vol. 132 Issue 3, p441 

    We have found that a brefeldin A (BFA)-resistant mutant cell line derived from Vero cells (BER-40) is highly resistant to ricin-induced apoptosis as compared with parental Vero cells. In BER-40 cells, all apoptotic events caused by ricin including cytolysis, nuclear morphological changes, and...

  • Characteristics of two cancer cell lines derived from metastatic foci in liver and peritoneum of a patient with colon cancer. Kotanagi, Hitoshi; Saito, Yuri; Yoshioka, Toshiaki; Koyama, Kenji; Kotanagi, H; Saito, Y; Yoshioka, T; Koyama, K // Journal of Gastroenterology;1998, Vol. 33 Issue 6, p842 

    Two cancer cell lines were established in vitro from a single patient with colon cancer; AKT-CC-K-LM cells from liver metastatic nodules and AKT-CC-K-PC cells from peritoneal dissemination nodules. The two cell lines were similar in doubling time, number of chromosomes, and chromosomal...

  • ß2-integrins mediate a novel form of chemoresistance in cycloheximide-induced U937 apoptosis. R.-C. Wu; Z. Wang; M.-J. Liu; D.-F. Chen; X.-S. Yue // Cellular & Molecular Life Sciences;Aug2004, Vol. 61 Issue 16, p2071 

    In this study with cycloheximide (CHX, an inhibitor of protein synthesis) and the human leukaemic cell line U937, a novel form of chemoresistance, which we termed sudden drug resistance (SDR), was identified using Hoechst33258 staining, Western blott and DNA Ladder. CHX high (10?100...

  • Interleukin-1β-Induced Promatrilysin Expression is Mediated by NFκB-Regulated Synthesis of Interleukin-6 in the Prostate Carcinoma Cell Line, LNCaP. Maliner-Stratton, Mimi Suzanne; Klein, Russell D; Udayakumar, Thirupandiyur S; Nagle, Raymond B; Bowden, George Timothy // Neoplasia;Nov2001, Vol. 3 Issue 6, p509 

    Previously, our laboratory showed that interleukin-1β (IL-1β) secreted by lipopolysaccharide-activated monocytes induces promatrilysin expression in the prostate carcinoma cell line, LNCaP. We now demonstrate that IL-1β-induced promatrilysin expression is mediated by an indirect...

  • Protective Effect of Melatonin on Methamphetamine-Induced Apoptosis in Glioma Cell Line. Jumnongprakhon, Pichaya; Govitrapong, Piyarat; Tocharus, Chainarong; Tungkum, Wanida; Tocharus, Jiraporn // Neurotoxicity Research;Apr2014, Vol. 25 Issue 3, p286 

    Methamphetamine (METH) is a highly addictive drug causing neurodegenerative diseases. METH has been known to be neurotoxic by inducing oxidative stress, free radical, and pro-inflammatory cytokines. Previous studies have shown that METH could induce neuron and glial cell death, especially...

  • Anisomycin induces glioma cell death via down-regulation of PP2A catalytic subunit in vitro. Li, Jun-yang; Huang, Jia-yuan; Li, Meng; Zhang, Han; Xing, Biao; Chen, Gong; Wei, Dong; Gu, Pei-yuan; Hu, Wei-xing // Acta Pharmacologica Sinica;Jul2012, Vol. 33 Issue 7, p935 

    Aim:To examine the effects of anisomycin on glioma cells and the related mechanisms in vitro.Methods:The U251 and U87 human glioblastoma cell lines were tested. The growth of the cells was analyzed using a CCK-8 cell viability assay. Apoptosis was detected using a flow cytometry assay. The...

  • Role and mechanism of Sophoridine on proliferation inhibition in human glioma U87MG cell line. Wen-Xin Wang; Zheng-Hui Sun; Han-Men Chen; Bai-Nan Xu; Fu-Yu Wang // International Journal of Clinical & Experimental Medicine;2015, Vol. 8 Issue 1, p464 

    Sophoridine, a natural product obtained from medicinal plants, which has a variety of pharmacological effects, including anti-cancer effects, and selectively induces apoptotic cell death in a variety of human cancer cells in vitro and in vivo; however, its mechanism of action needs to be further...

  • Knockdown of eukaryotic translation initiation factors 3B (EIF3B) inhibits proliferation and promotes apoptosis in glioblastoma cells. Liang, Hong; Ding, Xuehua; Zhou, Chun; Zhang, Yihua; Xu, Minhui; Zhang, Chengqu; Xu, Lunshan // Neurological Sciences;Oct2012, Vol. 33 Issue 5, p1057 

    Eukaryotic initiation factors 3 (EIF3) complex is essential for initiation of protein synthesis for both cells and virus. It consists of 13 subunits (EIF3A to M), among which EIF3B serves as a major scaffolding subunit. However, its functions in human glioblastoma have not been explored yet....


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics