Death receptors in chemotherapy and cancer

Debatin, Klaus‐Michael; Krammer, Peter H.

doi:10.1038/sj.onc.1207558

Cited by 458 publications

(361 citation statements)

References 280 publications

(268 reference statements)

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“…There are significant advantages in using combined therapy for cancer treatment. Since FasL expression and activity could be "naturally" restored in highly metastatic tumors through epigenetic and genetic changes [1,4,5], we have attempted to evoke FasL-mediated apoptotic death in Faspositive melanomas. Our first attempt was to modulate the FasL transcription [45,46,59,61,[86][87][88].…”

Section: Discussionmentioning

confidence: 99%

“…As a result, FasLFas-mediated apoptosis of cancer cells could be, in principle, a powerful strategy for anticancer therapy [14,15]. Unfortunately, in vivo, a number of problems are encountered such as severe systematic liver toxicity of FasL, FasL-based fusion proteins or agonistic anti-Fas monoclonal antibodies that greatly reduce the efficacy of these reagents in anticancer treatment, despite numerous attempts to overcome this problem over the past few years [1,53]. As an alternative to systemic treatment with FasL, an approach based on locally restricted upregulation of the membrane form of FasL on the surface of cancer cells could be a promising tool for induction of apoptosis among cancer cells [14].…”

Section: Fas Receptor and Fas Ligand Expression In Human Melanomasmentioning

confidence: 99%

“…Death receptors Fas (CD95/APO-1) and TRAIL Receptors-1 and-2 (DR4 and DR5) are present in a variety of tissues and play an important role in the regulation of general tissue homeostasis [1,2]. On the other hand, cancer development is often accompanied by the suppression of the surface Fas receptor expression and/or inactivation of the Fas-mediated signaling, potentially resulting in an inhibition of immuno-logical anticancer surveillance in vivo [3].…”

Section: Introductionmentioning

confidence: 99%

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Dual treatment with COX-2 inhibitor and sodium arsenite leads to induction of surface Fas Ligand expression and Fas-Ligand-mediated apoptosis in human melanoma cells

Ivanov¹,

Hei²

2006

Experimental Cell Research

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Most human melanomas express Fas receptor on the cell surface, and treatment with exogenous Fas Ligand (FasL) efficiently induces apoptosis of these cells. In contrast, endogenous surface expression of FasL is suppressed in Fas-positive melanomas. We report here the use of a combination of sodium arsenite, an inhibitor of NF-κB activation, and NS398, a cyclooxygenase-2 (COX-2) inhibitor, for restoration of the surface FasL expression. We observed a large increase of Fas-mediated apoptosis in Fas-positive melanomas. This was due to induction of FasL surface expression and increased susceptibility to Fas death signaling after arsenite and NS398 treatment. Furthermore, silencing COX-2 expression by specific RNAi also effectively increased surface FasL expression following arsenite treatment. Upregulation of the surface FasL levels was based on an increase in the efficiency of translocation to the cell surface and stabilization of FasL protein on the cell surface, rather than on acceleration of the FasL gene transcription. Data obtained demonstrate that the combination of arsenite with inhibitors of COX-2 may affect the target cancer cells via induction of FasL-mediated death signaling.

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Section: Discussionmentioning

confidence: 99%

Section: Fas Receptor and Fas Ligand Expression In Human Melanomasmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Dual treatment with COX-2 inhibitor and sodium arsenite leads to induction of surface Fas Ligand expression and Fas-Ligand-mediated apoptosis in human melanoma cells

Ivanov¹,

Hei²

2006

Experimental Cell Research

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“…The netrin-1 receptors DCC and UNC5H-1, -2 and -3, on the other hand, represent prototypic dependency receptors [23]. Activated death receptors induce the assembly of the death-inducing signaling complex (DISC), a molecular platform that promotes the dimerization and activation of initiator caspases-8 and -10 [24]. Similarly, the dependency receptors are probably connected to a rapid activation of the caspase cascade [23].…”

Section: Intrinsic and Extrinsic Apoptosis Pathwaysmentioning

confidence: 99%

Methods for the assessment of mitochondrial membrane permeabilization in apoptosis

et al. 2007

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Mitochondrial membrane permeabilization (MMP) is considered as the "point-of-no-return" in numerous models of programmed cell death. Indeed, mitochondria determine the intrinsic pathway of apoptosis, and play a major role in the extrinsic route as well. MMP affects the inner and outer mitochondrial membranes (IM and OM, respectively) to a variable degree. OM permeabilization culminates in the release of proteins that normally are confined in the mitochondrial intermembrane space (IMS), including caspase activators (e.g. cytochrome c) and caspase-independent death effectors (e.g. apoptosis-inducing factor). Partial IM permeabilization disrupts mitochondrial ion and volume homeostasis and dissipates the mitochondrial transmembrane potential ( m ). The assessment of early mitochondrial alterations allows for the identification of cells that are committed to die but have not displayed yet the apoptotic phenotype. Several

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“…These results led Melino to propose that the ratio of TAp73 to DNp73 may dictate the response to chemotherapy and suggest that TAp73 is the oncologist's friend, whereas DNp73 may prove to be the foe in tumorigenesis. 11 Orchestration of cell death: a tale of death receptors and mitochondria Apoptosis can be induced either by activation of death receptors or by perturbation of mitochondria [12][13][14] (Figure 2). G Cohen (Leicester, UK) explained how the mitochondrial pathway can be engaged in response to death receptor signalling, facilitating apoptosis by release from the mitochondria of cytochrome c or the inhibitor of apoptosis (IAP) antagonists Smac/Diablo and Omi/HtrA2.…”

Section: A Complex Decision Of Life or Deathmentioning

confidence: 99%