Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Cooperates with Anticancer Drugs to Overcome Chemoresistance in Antiapoptotic Bcl-2 Family Members Expressing Jurkat Cells

Ballestrero, Alberto; Nencioni, Alessio; Boy, Davide; Rocco, Ilaria; Garuti, Anna; Mela, Giuseppe Sandro; Parijs, Luk Van; Brossart, Peter; Wesselborg, Sebastian; Patrone, Franco

doi:10.1158/1078-0432.ccr-1365-02

Cited by 35 publications

(23 citation statements)

References 52 publications

(45 reference statements)

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“…In contrast, another report showed that TRAIL may overcome resistance in type I cells (Walczak et al, 2000). More light was shed onto this apparent discrepancy by a recent report where the effect of low or high doses of TRAIL was studied in Bcl-2-or Bcl-x L -overexpressing Jurkat cells (Ballestrero et al, 2004). There, Bcl-x L significantly inhibited induction of apoptosis by TRAIL at doses from 1 to 10 ng/ml, whereas higher doses of 50-100 ng/ml overcame Bcl-x L -mediated resistance to apoptosis.…”

Section: Discussionmentioning

confidence: 99%

TRAIL sensitizes for ionizing irradiation-induced apoptosis through an entirely Bax-dependent mitochondrial cell death pathway

et al. 2005

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The death ligand TRAIL has been suggested as a suitable biological agent for the selective induction of cell death in cancer cells. Moreover, TRAIL synergizes with DNAdamaging therapies such as chemotherapeutic drugs or ionizing irradiation (IR). Here, we show that synergy of TRAIL and IR, that is, crosssensitization between TRAIL and IR for induction of apoptosis, entirely depends on Bax proficiency in human DU145 and HCT116 carcinoma cells. DU145 prostate carcinoma cells that have lost Bax protein expression due to mutation fail to activate caspase-3 and -9 when exposed to TRAIL and IR. In contrast, TRAIL sensitized for IR-induced apoptosis and vice versa upon reconstitution of Bax expression. Notably, both DU145 and HCT116 still express significant levels of the multidomain proapoptotic Bcl-2 homolog Bak. This indicates that Bak is not sufficient to mediate crosssensitization and synergism between IR and TRAIL. These data clearly establish distinct roles for Bax and Bak in linking the TRAIL death receptor pathway to the mitochondrial apoptosis signaling cascade upon DNA damage by IR.

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Section: Discussionmentioning

confidence: 99%

TRAIL sensitizes for ionizing irradiation-induced apoptosis through an entirely Bax-dependent mitochondrial cell death pathway

et al. 2005

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“…Dead cells were enumerated by cell staining with 5 lg/ mL PI and flow cytometry [17,53]. The percentage of specific death was calculated as follows: 100 Â (experimental sample (%) -spontaneous sample (%)/100% -spontaneous sample (%)).…”

Section: Cell Viability Assaysmentioning

confidence: 99%

“…Flow-cytometric assay of DW m DW m determination was performed by incubating cells with 150 nM TMRE in regular medium at 37 C for 15 min and by subsequent flow-cytometric analysis as described [17,53].…”

Section: Digitonin Fractionation Of DCmentioning

confidence: 99%

Proteasome inhibitor‐induced apoptosis in human monocyte‐derived dendritic cells

et al. 2006

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Proteasome inhibitors possess potent antitumor activity against a broad spectrum of human malignancies. However, the effects of these compounds on the immune system still have to be clearly determined. In the present study, we have investigated the effects of proteasome inhibitors on dendritic cells (DC), antigen‐presenting cells playing a key role in the initiation of immune responses. Exposure to the proteasome inhibitors bortezomib, MG132 or epoxomicin was found to promote apoptosis of human monocyte‐derived DC and to reduce the yield of viable DC when given to monocytes early during differentiation to DC. DC apoptosis via proteasome inhibition was accompanied by mitochondria disruption and subsequent activation of the caspase cascade. Up‐regulation and intracellular redistribution of Bcl‐2‐associated X protein (Bax), a pro‐apoptotic Bcl‐2 family protein, were observed in DC treated with these compounds and represent a suitable mechanism leading to activation of the intrinsic apoptotic pathway. Finally, active protein synthesis was found to represent an upstream prerequisite for DC apoptosis induced by proteasome inhibitors, since the translation inhibitor cycloheximide blocked all of the steps of the observed apoptotic response. In conclusion, induction of apoptosis in DC may represent a novel mechanism by which proteasome inhibitors affect the immune response at the antigen‐presenting cell level.

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“…Collectively, these Cyr61 has been recognized as an effective molecule in inducing resistance of cancer cells to various chemotherapeutic drugs (Marra et al 2009). TRAIL has also been identified as a promising candidate for overcoming chemoresistance in tumor cells by activating the caspase cascade directly as well as its ability to induce a synergistic induction of apoptotic cell death when combined with other anticancer drugs (Ballestrero et al 2004). In this study, Cyr61 silencing effectively enhanced apoptotic cell death induced by TRAIL.…”

Section: Discussionmentioning

confidence: 70%

Knockdown of cysteine-rich 61 inhibits proliferation, migration, and invasiveness of prostate carcinoma PC-3 cells

Lee

Jeong

et al. 2013

Animal Cells and Systems

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The overexpression of wild-type cysteine-rich 61 (Cyr61) is associated with the aggressiveness of cancer and poor prognosis in different human cancers. The aim of this study was to examine the expression of Cyr61 protein in prostate adenocarcinomas and to investigate the effects of inhibiting Cyr61 expression using small interfering RNA on the proliferation, migration, invasiveness, and sensitivity of prostate carcinoma PC-3 cells to TNF-related apoptosis-inducing ligand. Cell proliferation was measured by XTT assay. Colony formation assay, wound healing assay, and Matrigel invasion assay were also examined. Immunohistochemical staining of prostate tumor tissues showed that prostate carcinomas had significantly increased Cyr61 level compared with benign glands adjacent to carcinoma. siRNA-based knockdown of Cyr61 resulted in decreased cellular proliferation, clonogenicity, migration, and invasion. At the same time, Cyr61 silencing effectively reduced the levels of phosphorylated Akt and integrin-b 3 . Cyr61-specific siRNA combined with TRAIL increased the apoptosis of PC-3 cells and the cleavage of apoptosis hallmarkers such as PARP and caspase-3. Taken together, our data provide evidence that Cyr61 modulates integrinb 3 level as well as PI3-kinase/Akt activity through which Cyr61 may mediate tumorigenesis, and suggest the potential importance of Cyr61 targeting on enhancing the therapeutic efficacy of prostate cancer.

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Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Cooperates with Anticancer Drugs to Overcome Chemoresistance in Antiapoptotic Bcl-2 Family Members Expressing Jurkat Cells

Cited by 35 publications

References 52 publications

TRAIL sensitizes for ionizing irradiation-induced apoptosis through an entirely Bax-dependent mitochondrial cell death pathway

TRAIL sensitizes for ionizing irradiation-induced apoptosis through an entirely Bax-dependent mitochondrial cell death pathway

Proteasome inhibitor‐induced apoptosis in human monocyte‐derived dendritic cells

Knockdown of cysteine-rich 61 inhibits proliferation, migration, and invasiveness of prostate carcinoma PC-3 cells

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