Induction of Apoptosis in Glioma Cells by Recombinant Human Fas Ligand

Kawaguchi, Shojiro; Mineta, Toshihiro; Ichinose, Makoto; Masuoka, Jun; Shiraishi, Tetsuya

doi:10.1097/00006123-200002000-00030

Cited by 17 publications

(9 citation statements)

References 40 publications

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“…The reactivity of recombinant porcine FasL with anti-human FasL antibody was greatly reduced under a reducing condition, suggesting that porcine FasL has little stability, as previously reported in mouse FasL by Mariani et al (22) The baculovirus expression system has been used successfully for mouse and human recombinant FasL production. (22,23) Our results were consistent with the findings of these previous reports.…”

Section: Discussionsupporting

confidence: 93%

Molecular Cloning, Characterization, and Expression of Porcine Fas Ligand (CD95 Ligand)

Muneta

Shimoji²,

Inumaru³

et al. 2001

Journal of Interferon & Cytokine Research

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We isolated and sequenced cDNA that contained the coding sequence of porcine Fas ligand (FasL). Using mixed oligonucleotide primers based on the 5' and 3' nucleotide sequences conserved among human, murine, and rat FasL, we performed the reverse transcription polymerase chain reaction (RT-PCR) with total RNA prepared from porcine thymocytes stimulated with 5 microg/ml concanavalin A (ConA) to clone the cDNA of porcine FasL. The open reading frame (ORF) of porcine FasL cDNA was 849 base pairs (bp) in length and encoded 282 amino acids. The predicted amino acid sequence was 85.5%, 76.6%, and 75.5% homologous to the predicted human, murine, and rat FasL, respectively. The recombinant porcine FasL expressed by recombinant baculovirus containing the whole coding sequences of porcine FasL showed cytotoxic effect and induced apoptosis in porcine renal tubular cell line PK-15 cells sensitized by cycloheximide (CHX), which was confirmed by MTT assay, DNA fragmentation assay, and TUNEL staining, respectively. Furthermore, the mRNA expression of porcine FasL in porcine peripheral blood lymphocytes (PBL) was induced by porcine interleukin-18 (IL-18). These results indicate that porcine FasL identified in this study is biologically functional and has the ability to induce apoptosis as reported in other species.

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Section: Discussionsupporting

confidence: 93%

Molecular Cloning, Characterization, and Expression of Porcine Fas Ligand (CD95 Ligand)

Muneta

Shimoji²,

Inumaru³

et al. 2001

Journal of Interferon & Cytokine Research

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“…[21][22][23][24] Recently, studies have shown that both FasL and TRAIL can induce apoptosis in a number of tumor cell lines of various origins. [25][26][27][28][29] These proteins may have an advantage as therapeutics for brain tumors (BTs), since both they and their receptors are membrane proteins. Death ligand-induced apoptosis is mediated through cellcell contact, allowing the cell expressing the ligand to induce apoptosis in a number of surrounding receptorexpressing cells -a bystander effect not directly achieved with intracellular apoptosis-inducing proteins like p53 and Bax, and which does not require transport of prodrugs across the blood-brain barrier, as is the case for TK and cytosine deaminase.…”

mentioning

confidence: 99%

“…Several published reports describe the construction and analysis of replication-defective recombinant Ad vectors that deliver FasL 25,27,[30][31][32][33][34] or TRAIL. 35,36 These vectors have not been uniformly successful against tumors established in animal models.…”

mentioning

confidence: 99%

“…35,36 These vectors have not been uniformly successful against tumors established in animal models. 25,27,[37][38][39] Lack of efficacy has generally been blamed on the acquired resistance of many tumor isolates to FasL-or TRAIL-mediated apoptosis. However, problems with vector delivery, sufficiently high transgene expression levels and the stability of the expressed protein may also play a significant role.…”

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confidence: 99%

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Enhanced apoptosis of glioma cell lines is achieved by co-delivering FasL-GFP and TRAIL with a complex Ad5 vector

Rubinchik

Woraratanadharm

et al. 2003

Cancer Gene Ther

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Brain tumors (BTs) are among the most malignant forms of human cancer. Unfortunately, current treatments are often ineffective and produce severe side effects. Cytotoxic gene therapy is an alternative treatment strategy, with the potential advantages of reduced toxicity to normal brain tissue. Apoptosis-inducing ''death ligands'' Fas ligand and TNF-related apoptosis-inducing ligand (TRAIL) are genes with substantial cytotoxic activity in susceptible tumor cells. Here, we compared the effectiveness of Ad vectormediated delivery of Fas ligand-green fluorescent protein (FasL-GFP) fusion protein, human TRAIL, and both genes simultaneously. We examined a panel of 13 cell lines (eight derived from primary isolates) for susceptibility to Ad5-based vector infection and for sensitivity to FasL-and TRAIL-mediated apoptosis. All cell lines were efficiently transduced, but, as expected, varied in their sensitivity to ligand-induced apoptosis. Generally, sensitivity to FasL-GFP correlated with cell surface FasR levels, but no such correlation was seen for TRAIL and its functional receptors, DR4 and DR5. The vector expressing both FasL-GFP and TRAIL was more effective than either of the single-gene vectors at comparable transduction levels, and it was effective against a broader range of cell lines. In five cell lines, coexpression resulted in apoptosis levels greater than those predicted for strictly additive activity of the two death ligands. We believe that Ad vector-mediated delivery of multiple death ligands may be developed as a potential BT therapy, either alone or in conjunction with surgical resection of the primary tumor.

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“…Human gliomas are highly resistant to current therapeutic approaches, including radiation and chemotherapy that often induce cell death via Fas-FasL system. The application of recombinant FasL (Kawaguchi et al, 2000) or adenovirus-mediated transduction of FasL induces apoptosis of malignant glioma cells (Shinoura et al, 1998;Ambar et al, 1999), which suggests an impairment in the initiation rather than in the executory phase of Fas-mediated apoptosis in glioma cells.…”

Section: Involvement Of Akt/forkhead Pathway and Fasl Expression In Gmentioning

confidence: 99%

Inhibition of Akt kinase signalling and activation of Forkhead are indispensable for upregulation of FasL expression in apoptosis of glioma cells

et al. 2003

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Induction of Apoptosis in Glioma Cells by Recombinant Human Fas Ligand

Abstract: The present results suggest that the induction of apoptosis by the Fas/FasL system could be a new strategy for the treatment of malignant brain tumors, which are resistant to conventional therapies.

Cited by 17 publications

References 40 publications

Molecular Cloning, Characterization, and Expression of Porcine Fas Ligand (CD95 Ligand)

Molecular Cloning, Characterization, and Expression of Porcine Fas Ligand (CD95 Ligand)

Enhanced apoptosis of glioma cell lines is achieved by co-delivering FasL-GFP and TRAIL with a complex Ad5 vector

Inhibition of Akt kinase signalling and activation of Forkhead are indispensable for upregulation of FasL expression in apoptosis of glioma cells

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