TRAIL, Fasl and a blocking anti-DR5 antibody augment paclitaxel-induced apoptosis in human non-small-cell lung cancer

Odoux, Christine; Albers, Andreas E.; Amoscato, Andrew A.; Lotze, Michael T.; Wong, Michael K.

doi:10.1002/ijc.1640.abs

Cited by 9 publications

(12 citation statements)

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“…In their study, apoptosis was also inhibited by anti-Fas-L antibodies and absent in mutant Fas cell lines [27]. These observations are in contrast with results reported in lung cancer where neither Fas-L-blocking antibodies could protect cells from apoptosis nor could a modulation of Fas/Fas-L expression be detected after paclitaxel exposure [28, 29]. However, these studies demonstrated an involvement of caspases 3 and 8 in paclitaxel-induced cell death.…”

Section: Discussioncontrasting

confidence: 55%

“…An involvement of the Fas-L signaling pathway in drug-induced apoptosis is in accordance with some results from studies of leukemia as well as solid tumors [3, 18, 19, 30, 31]but in contrast with other reports [5, 28, 29, 32]. This discrepancy may be due to heterogenous cell type-dependent expression of several other death signal proteins such as TRAIL, Apo-3, TNF-α and their cognate receptors [8, 29, 33, 34], as well as apoptosis-regulating factors, i.e.…”

Section: Discussioncontrasting

confidence: 54%

“…However, these studies demonstrated an involvement of caspases 3 and 8 in paclitaxel-induced cell death. In addition, Odoux et al [29]demonstrated that antibody-induced cross-linking of Fas-L significantly amplifies paclitaxel-induced apoptosis in non-small cell lung cancer, probably due to activation of caspases.…”

Section: Discussionmentioning

confidence: 99%

“…This discrepancy may be due to heterogenous cell type-dependent expression of several other death signal proteins such as TRAIL, Apo-3, TNF-α and their cognate receptors [8, 29, 33, 34], as well as apoptosis-regulating factors, i.e. p53, bcl and bax proteins [18, 25, 27].…”

Section: Discussionmentioning

confidence: 99%

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Paclitaxel Treatment of Breast Cancer Cell Lines Modulates Fas/Fas Ligand Expression and Induces Apoptosis Which Can Be Inhibited through the CD40 Receptor

Stumm

Meyer

Lindner³

et al. 2004

Oncology

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Objective: Cytotoxic chemotherapy of advanced breast cancer is frequently complicated by drug resistance. Our goal was to define the role of the apoptosis-regulating receptors Fas (CD95) and CD40 in the chemosensitivity of breast cancer. Methods: The sensitivity of four breast cancer cell lines to paclitaxel and mitoxantrone was evaluated using an ATP-based cell viability assay. After verification of apoptosis by annexin V staining and TUNEL assay, cell lines were characterized regarding their constitutive expression of both surface and soluble (s)Fas (CD95) and Fas ligand (Fas-L). The role of the Fas/Fas-L system and different caspases was assessed by blocking drug-mediated apoptosis with specific antibodies. Finally, the paclitaxel sensitivity of the CD40-negative cell line KS was compared to that of its CD40-positive transfectant KS-CD40. Results and Conclusion: While the cytotoxic effect of mitoxantrone did not correlate with Fas expression, the results presented here suggest some involvement of the Fas/Fas-L system in paclitaxel-induced apoptosis. Cell lines with constitutive expression of Fas/sFas demonstrated a higher sensitivity to paclitaxel than Fas-negative cells. Incubation with paclitaxel led to a measurable downregulation of the expression of both soluble and surface Fas receptor in these cells. Interestingly, stimulation of the CD40 receptor inhibited paclitaxel-induced apoptosis in the transfected cell line KS-CD40, suggesting a role of this receptor in the modulation of chemosensitivity.

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Section: Discussioncontrasting

confidence: 55%

Section: Discussioncontrasting

confidence: 54%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Paclitaxel Treatment of Breast Cancer Cell Lines Modulates Fas/Fas Ligand Expression and Induces Apoptosis Which Can Be Inhibited through the CD40 Receptor

Stumm

Meyer

Lindner³

et al. 2004

Oncology

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“…This indicates that chemotherapy may enhance TRAIL-induced cell death in some breast cancers. Paclitaxel-induced apoptosis was also enhanced by FasL and TRAIL in non-small cells lung cancer (NSCLC) [166]. In addition, camptothecin and cisplatin were synergistic with TRAIL [167].…”

Section: Direct Activation Of Cell Death Pathways With Death Ligandsmentioning

confidence: 99%

Molecular Targeting of Cell Death Signal Transduction Pathways in Cancer

Peták¹,

Houghton²,

Kopper

2006

CST

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Suppression of cell death (most often apoptosis) by survival signals, or by defects in cell death signal transduction pathways, is considered one of the obligate hallmarks of malignant transformation. However, molecular survival strategies to evade cell death only have relevance in the presence of pro-death signals. Discovery of the apoptotic properties of oncogenes responsible for increased tumor cell proliferation (e.g. c-Myc) provided the most important example for such signals and led to the concept of synthetic lethal targeting as a strategy of identifying cancer specific drug target molecules. Besides growth signal autonomy, other hallmarks of oncogenesis (insensitivity to anti-growth signals, limitless replicative potential, invasion and metastasis, angiogenesis and increased genomic instability) are also challenged by increased susceptibility to various forms of cell death. Therefore, cancer cells must acquire survival strategies to suppress these cell death/apoptosis mechanisms. Novel signal transduction therapies can target molecules involved in these strategies to trigger tumor specific cell death.

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A novel humanized anti‐tumor necrosis factor‐related apoptosis‐inducing ligand‐R2 monoclonal antibody induces apoptotic and autophagic cell death

et al. 2017

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It is well known that the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/TNFSF10) is specifically expressed in various tumor cells, but less or no expression in most normal tissues and cells. While TRAIL engages with its native death receptors, TRAIL receptor 1 (TRAIL-R1) or 2 (TRAIL-R2), usually elicits the tumor cell death by apoptosis. In this study, we report that a novel humanized monoclonal antibody against TRAIL-R2 (named as zaptuzumab) well remain the biological activity of the parental mouse antibody AD5-10 inducing cell death in various cancer cells, but little effect on normal cells. Zaptuzumab also markedly inhibited the tumor growth in the mouse xenograft of NCI-H460 without toxicity to the liver and kidney, and the efficacy of tumor suppression was increased significantly while it combined with cis-dichlorodiamineplatinum. Especially, I-labeled zaptuzumab injected into mouse tail vein specifically targeted to the xenograft of the lung cancer cells. Confocal analysis showed that zaptuzumab bound with TRAIL-R2 on cell surface could be quickly internalized and transferred into the lysosome. Furthermore, zaptuzumab possessed a high level of antibody-dependent cytotoxicity as well as complement-dependent cytotoxicity. Study on the mechanisms of cell death induced by zaptuzumab showed that it efficiently induced both caspase-dependent apoptosis and autophagic cell death. These data suggest that the humanized anti-TRAIL-R2 monoclonal antibody or the second generation of the antibody may have an important clinical usage for cancer immunotherapy. © 2017 IUBMB Life, 69(9):735-744, 2017.

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TRAIL, Fasl and a blocking anti-DR5 antibody augment paclitaxel-induced apoptosis in human non-small-cell lung cancer

Cited by 9 publications

References 0 publications

Paclitaxel Treatment of Breast Cancer Cell Lines Modulates Fas/Fas Ligand Expression and Induces Apoptosis Which Can Be Inhibited through the CD40 Receptor

Paclitaxel Treatment of Breast Cancer Cell Lines Modulates Fas/Fas Ligand Expression and Induces Apoptosis Which Can Be Inhibited through the CD40 Receptor

Molecular Targeting of Cell Death Signal Transduction Pathways in Cancer

A novel humanized anti‐tumor necrosis factor‐related apoptosis‐inducing ligand‐R2 monoclonal antibody induces apoptotic and autophagic cell death

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