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Bortezomib inhibits NFKBIA. 47 / 48
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"We found that the combination treatment of an XPO1 inhibitor (selinexor) and a PI (bortezomib) synergistically increased IkappaBalpha more than single-agent selinexor or bortezomib treatment in both parental and PI resistant MM cell lines and in patient myeloma cells."
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"The observation that bortezomib reduced IkB-alpha levels in human glioma cells is novel and, these findings are consistent with previous studies demonstrating that PS-341 as well other proteasome inhibitors induce IkB-alpha degradation in endometrial carcinoma cell lines, HepG2 liver cancer cell line, multiple myeloma cells and other tumor types."
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"Conversely, bortezomib downregulated IkappaBalpha at early time points (XREF_FIG)."
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"The autophagy inhibitor chloroquine (CQ) significantly inhibited bortezomib induced I-kappaBalpha degradation, increased complex formation with NF-kappaB and reduced NF-kappaB nuclear translocation and DNA binding activity."
22393418
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"However , in MM cell lines and primary tumor cells from MM patients , bortezomib significantly down-regulated IkappaBalpha expression and induced NF-kappaB activation [ 135 ] ."
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"On the opposite, bortezomib induces the calpain dependent degradation of IkappaBalpha by activating the ubiquitous calpains."
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"This conclusion is based on our data showing that impairment of lysosomal acidification by the V-ATPase inhibitor BafA1 prevents ST80 and Bortezomib stimulated IkappaBalpha degradation, NF-kappaB activation and BAG3 upregulation."
25766331
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"Bortezomib downregulates the IkappaBalpha protein."
24481412
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"Previous studies demonstrated that degradation of IkappaBalpha by Bortezomib leads to NF-kappaB activation [XREF_BIBR, XREF_BIBR]."
| PMC
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"Bortezomib was shown to activate IKKbeta and decrease the abundance of IkappaBalpha, thereby increasing canonical NF-kB activity in myeloma cells; 23 however, this was not reproducible in T-ALL cells."
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"To this end, Hut-78 cells were transfected with non silencing or IkappaBalpha siRNA, treated with increasing concentrations of bortezomib as described above, and apoptosis was measured by a quantitative ELISA assay based on the detection of nucleosome release into the cytoplasm."
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"We demonstrate that bortezomib induces I-kappaBalpha degradation which is removed by the autophagic process and activates NF-kappaB transcriptional activity."
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"In our study, Bortezomib degraded not only IkappaBalpha protein but also the p65 subunit of NF-kappaB."
| PMC
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"We found that Bortezomib degrades p65 and IkappaBalpha through different mechanisms."
| PMC
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"Inhibition of IKKbeta blocks bortezomib induced IkappaBalpha down-regulation and NF-kappaB activation."
24481412
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"Since we observed that ST80 and Bortezomib cotreatment triggers the degradation of IkappaBalpha (XREF_FIG), we next asked how IkappaBalpha is degraded when the proteasome is inhibited by Bortezomib."
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"Taken together, these results demonstrate that bortezomib induces canonical NF-kappaB activation by triggering the autophagic degradation of I-kappaBalpha."
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"Blocking autophagy by CQ potentiates bortezomib induced accumulation of I-kappaBalpha and DLBCL cell death."
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"We have shown that fenretinide reduces expression of IKK, which may to some degree abrogate the effect that bortezomib has on calpain mediated degradation of IkappaBalpha."
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"Bortezomib , a proteasomal inhibitor [ 118 ] , which inhibits IkappaBalpha degradation and p65 nuclear accumulation [ 119 ] , counteracted virally induced p65 nuclear protein expression in U266 nuclear extracts ."
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"It has been shown that bortezomib inhibits proteasomal degradation of IkappaBalpha induced by cytokines (i.e., TNFalpha); however, IkappaBalpha was downregulated in both cell lines by bortezomib treatment, associated with enhanced phosphorylation in breast cancer cells."
24481412
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"Hideshima et al. found that bortezomib triggers the canonical pathway of NF-kappaB and downregulates IkappaBalpha in primary cells from patients with MM."
26075279
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"This suggests that bortezomib induced I-kappaBalpha degradation is not occurring through the UPS pathway XREF_BIBR."
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"However, our results demonstrated that treatment with bortezomib induced I-kappaBalpha degradation in DLBCL cell lines as well as in primary FL and DLBCL cells, in agreement with the finding by Hideshima and colleagues in multiple myeloma cells XREF_BIBR."
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"So the decreased IkappaB-alpha protein level in JurkatB5 cells treated with bortezomib indicated an upregulation of NF-kappaB activity after bortezomib treatment, resulting in the suppression of apopt[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
18562081
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"In the presence of bortezomib, CQ prevented bortezomib induced I-kappaBalpha degradation but not I-kappaBalpha phosphorylation."
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"Bortezomib induced I-kappaBalpha degradation decreased its complex formation with NF-kappaB and increased NF-kappaB nuclear translocation and therefore its DNA binding activity."
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"Interestingly, inhibition of lysosomal activity by Bafilomycin A1 inhibits ST80 and Bortezomib stimulated IkappaBalpha degradation, NF-kappaB activation and BAG3 upregulation, indicating that IkappaBalpha is degraded via the lysosome in the presence of Bortezomib."
25766331
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"Correction : Proteasome inhibitor PS-341 (bortezomib) induces calpain dependent IkappaBalpha degradation."
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"In line with our observations, another study demonstrated differential effects of bortezomib on NFkappaB activity depending on different cell types : bortezomib triggered NFkappaB activity via the canonical pathway in peripheral blood mononuclear cells by enhancing non proteosomal degradation of IkappaBalpha while NFkappaB activation was inhibited in bone marrow derived stromal cells [39]."
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"Many studies have demonstrated that bortezomib prevented IkappaBalpha from degradation by proteasome, thus inhibiting nuclear translocation of NF-kappaB, cytokine circuits and the survival advantage for MM cells conferred by the BM microenvironment [XREF_BIBR, XREF_BIBR, XREF_BIBR]."
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"14 Intriguingly, addition of BafA1 attenuated the ST80 and Bortezomib triggered degradation of IkappaBalpha protein, whereas it did not block NIK accumulation, phosphorylation of IkappaBalpha and p65 or acetylation of histone H3 (XREF_FIG)."
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"In summary, here we report, for the first time, that bortezomib induced I-kappaBalpha degradation in DLBCL cells may be due to activated autophagy."
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"We therefore tested whether bortezomib induced I-kappaBalpha degradation also occurs in DLBCL cells and whether this degradation is associated with enhanced autophagy."
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"The proteosomal inhibitor, bortezomib, suppresses NF-kappaB signaling by preventing IkappaBalpha degradation and is reported to reduce synovial macrophage inflammatory activity in experimental murine collagen arthritis [XREF_BIBR] but, again, is not specifically targeted to the macrophage."
21324111
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"Bortezomib reversibly targets the chymotrypsin like activity of the proteasome and blocks the degradation of the NF-kappaB inhibitory protein IkappaBalpha."
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"As reported by many clinical trials, bortezomib alone or in combination with other drugs has dramatically improved the outcomes for patients with relapsed MM, which was in accordance with experimental results showing that bortezomib inhibited NF-kappaB activation in MM cells by blocking IkappaBalpha degradation in the proteasome."
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"Bortezomib induced I-kappaBalpha degradation was also observed in primary FL and DLBCL cells (XREF_FIG)."
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"Bortezomib prevented LMP-1 induced proteasomal degradation of IkappaBalpha leading to the suppression of the NF-kappaB signaling pathway."
39325843
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"The proteasome inhibitor Bortezomib ( Velcade ) is able to block IkappaBalpha degradation , a key step for NF-kappaB release [ 177 ] ."
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"While our previous results showed that Bortezomib inhibits TNF induced degradation of IkappaBalpha protein (XREF_FIG), we paradoxically found that Bortezomib by itself induced the degradation of IkappaBalpha in a dose (XREF_FIG) and time dependent manner (XREF_FIG)."
| PMC
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"Our results demonstrate that bortezomib induced IkappaBalpha degradation occurred in conjunction with the activation of caspase-8; moreover, the decrease in IkappaBalpha level was prevented in a dose dependent manner by the addition of z-IETD, a specific inhibitor of caspase-8."
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"By inhibiting the degradation of cytoplasmic IkappaBalpha, bortezomib inhibits the activation of NF-kappaB."
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"Immuno precipitation results showed that bortezomib reduced the interaction between NF-kappaB RelA and p65 and I-kappaBalpha and co-treatment with CQ prevented bortezomib induced disruption of NF-kappaB and I-kappaBalpha binding (XREF_FIG)."
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"Because Bortezomib induced degradation of IkappaBalpha, we investigated whether this proteasome inhibitor by itself can activate NF-kappaB in leukemia cells."
| PMC
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"At first, it was thought that bortezomib prevented IkappaBalpha from degradation and inhibited the nuclear factor kappa B (NF-kappaB) pathway in myeloma [XREF_BIBR]."
29518205
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"Our data suggest that bortezomib treatment not only induces IkappaB-alpha degradation, NF-kappaB inhibition and independent apoptosis induction, but also strongly enhances TRAIL mediated cytotoxicity in malignant human glioma cell lines."
21220502