NF-κB Potentiates Caspase Independent Hydrogen Peroxide Induced Cell Death

Ho, Jessica Q.; Asagiri, Masataka; Hoffmann, Alexander; Ghosh, Gourisankar

doi:10.1371/journal.pone.0016815

Cited by 15 publications

(10 citation statements)

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“…Moreover, a PARP inhibitor was found to inhibit p38 expression and cause the phosphorylation of retinal neurons in mice model of chronic hypoperfusion and chorionic cells in chicks. 8,9 It has also been reported that inhibiting PARP could adjust p38 10 and that ERK phosphorylation of the MAPK pathway, could then downregulate nuclear factor (NF)-kB transcriptional 11 activity and consequently decrease the expressions of NF-kB-dependent genes such as intercellular cell adhesion molecule (ICAM-1), which is important during inflammatory processes. As, our previous results also demonstrated that inhibiting PARP could inhibit NF-kB activity in mice colon cancer CT26 cells; 12 vascular endothelial growth factor (VEGF), b-FGF (basic fibroblast growth factor), ICAM-1 and matrix metalloproteinases (MMP)-9 being well known NF-kB-dependent angiogenic-related factors, reflecting the relative migratory and proliferative ability of tumors were assessed in our experimental trial.…”

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confidence: 99%

Effect of silencing PARG in human colon carcinoma LoVo cells on the ability of HUVEC migration and proliferation

Pan

Wang

et al. 2012

Cancer Gene Ther

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Our aim was to investigate the influence of silencing poly-(ADP-ribose)glycohydrolase (PARG) in human colon carcinoma LoVo cells on the ability of human umbilical vein endothelial cell (HUVEC) migration, proliferation and its possible mechanisms. PARG mRNA expression was detected by reverse transcriptase (RT) and real-time-PCR. PARG, poly-(ADP-ribose)polymerase (PARP), p38, p-p38, extracellular signal-regulated kinase (ERK), p-ERK, nuclear factor (NF)-kB, phosphorylated IkBa (p-IkBa), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (b-FGF), intercellular cell adhesion molecule (ICAM)-1 and matrix metalloproteinases (MMP)-9 expressions were detected by western blot. The influence of PARG-short hairpin (sh)RNA on the ability of HUVEC migration and proliferation were observed by transwell migration and Counting Kit-8 (CCK-8) assay. Both RT-PCR and western blot results showed that the expression of PARG in PARG-shRNA cells was decreased and expressions of PARP, p38, p-p38, ERK, p-ERK, NF-kB, p-IkBa, VEGF, b-FGF, ICAM-1 and MMP-9 in those cells were lower than that in the untransfected and control-shRNA groups (Po0.05). Migration assay showed that migratory inhibition rate for HUVEC was decreased (55.23%) in cocultured PARG-shRNA cells; moreover, CCK-8 assay showed that the proliferation of HUVECs cultured with the supernatant of PARG-shRNA cells was also comparatively lower. Hence, concluding that PARG silencing could inhibit the ability of HUVEC migration and proliferation by downregulating the activity of NF-kB in LoVo cells that in turn decreases angiogenic factors such as VEGF, b-FGF, ICAM-1, MMP-9, as well as phosphorylation of p38 and ERK.

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confidence: 99%

Effect of silencing PARG in human colon carcinoma LoVo cells on the ability of HUVEC migration and proliferation

Pan

Wang

et al. 2012

Cancer Gene Ther

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“…Thus, taking in to account on the DNA damage induced by isothiacalothrixin B and subsequent arrest of cells in G1 and G2/M phase, without an increase in the protein levels of p53 strongly support the notion that the induction of cell death is p53- independent. Several studies have highlighted the p53-independent induction of cell death following DNA damage mediated through the pro-apoptotic p73 [ 43 , 44 ] or NF-kB (nuclear factor-kB) [ 45 , 46 ] or by the degradation of anti-apoptotic protein BCL2 [ 47 ], and thus it is possible that isothiacalothrixin B analogues caused cell death through any of these mechanisms. Both the thiacalothrixin B and calothrixin B induced accumulation of p21 waf1/cip1 protein.…”

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confidence: 99%

Novel isothiacalothrixin B analogues exhibit cytotoxic activity on human colon cancer cells in vitro by inducing irreversible DNA damage

et al. 2018

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Preliminary cytotoxic analysis of sulphur containing isosteric analogues of calothrixin B identified the useful anti-tumour activity of thia/isothiacalothrixin B which necessitated it’s biological evaluation in colon and lung cancer cell lines. The isothia analogues induced cytotoxicity of HCT116 in a time-dependent manner and inhibited the clonogenic survival of HCT116 and NCI-H460 cells in a dose-dependent manner comparable to the standard anti-cancer drug camptothecin. Herein employing flow cytometry, we demonstrate that isothiacalothrixin B analogues inhibited proliferation of colon cancer cells by the arrest of cells in S and G2/M phases over a period of 48 hours at a concentration of 5 μM. Our results also suggest that the cytotoxicity of thia analogues of calothrixin B is partially mediated by induction of cellular DNA strand breaks. The UV-Vis spectroscopic studies with CT-DNA revealed groove binding for calothrixin B and its thia analogues wherein subsequent in silico molecular modelling studies indicated preferential binding to the AT-rich regions of minor groove of DNA. Furthermore, thiacalothrixin B caused transcriptional activation of p21waf1/cip1 promoter and upregulation of its protein levels independent of p53. The induction of DNA damage response pathway leads to apoptosis in isothiacalothrixin B but not in thiacalothrixin B treated cells. The isothia analogues SCAB 4 induced DNA strand breaks and cell cycle arrest even after treatment for a short period (i.e., 4 hours) and the cell cycle effects were irreversible. For the first time, this study provides detailed cellular effects on the potential use of isothiacalothrixin B analogues as cytotoxic agents.

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“…[30][31][32] In the caspase-independent pathway, nuclear factor-kappa B (NF-κB), p53, p73 and orphan nuclear receptor Nur77 are reportedly involved in apoptosis. [33][34][35][36] One limitation of this study is the fact that it was conducted in vitro. Moreover, in a clinical setting, MTMP that is present in an infusion bag slowly enters the body in small amounts over an extended period of time.…”

Section: Discussionmentioning

confidence: 99%

The Polymerization Agent, 2-Methyl-4′-(methylthio)-2-morpholinopropiophenone Induces Caspases-3/7 in Human Blood Mononuclear Cells <i>in Vitro</i>

Kawasaki

Yagi

Tsuboi

et al. 2013

Biological & Pharmaceutical Bulletin

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Our previous studies detected the presence of a photoinitiator 2-methyl-4′-(methylthio)-2-morpholinopropiophenone (MTMP) in an intravenous (i.v.) injection bag solution. Importantly, MTMP has demonstrated cytotoxicity for normal human peripheral blood (PB) mononuclear cells (MNC). Cell death pathways have two well-known modes, apoptosis and necrosis. But it has not been clear whether MTMP induced apoptosis or necrosis in normal human PB MNC. In the present in vitro study, we examined normal human PB MNC for the frequencies of apoptosis and necrosis and changes upon exposure to MTMP. We observed time-dependent changes in MNC viability with MTMP. We also assessed the activity of caspases-3/7. The results demonstrated that MTMP induced apoptosis in normal human PB MNC after 24 h. In addition, MTMP induced caspases-3/7 in a time-dependent manner. In conclusion, we suggest that MTMP induces apoptosis in a caspase-dependent pathway in vitro.Key words photoinitiator; apoptosis; caspase-3; caspase-7; cytotoxicity; human mononuclear cell Photoinitiators are used in a broad range of commercial and biological applications such as printing, 1) dentistry, 2) encapsulation of pancreatic islet cells, 3,4) and blood vessel adhesives.5) Thus, a high level of daily exposure to photoinitiators is possible. In previous in vitro studies, it was reported that photopolymerizing agents were cytotoxic. The photoinitiators Sarcat CD 1012, Araidite GY 281 and Epon 825 were cytotoxic to L929 cells, 6) and 4-octylphenyl phenyliodoniumhexafluoroantimonate (OPIA) also was severely cytotoxic.7) In other studies, Irgacure 2959 was found to be the least toxic photoinitiator while 1-hydroxycyclohexyl phenyl ketone (Irgacure 184) and 2,2-dimethoxy-2-phenylacetophenone (Irgacure 651) were significantly more toxic to human fetal osteoblasts. 8)In our recent study, we detected the presence of the photoinitiator 2-methyl-4′-(methylthio)-2-morpholinopropiophenone (MTMP) at approximately 2.8 mg/bag (5.6 µg/mL) in an intravenous (i.v.) injection bag solution. We demonstrated that MTMP was cytotoxic to normal human peripheral blood (PB) mononuclear cells (MNC). 9)

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NF-κB Potentiates Caspase Independent Hydrogen Peroxide Induced Cell Death

Cited by 15 publications

References 50 publications

Effect of silencing PARG in human colon carcinoma LoVo cells on the ability of HUVEC migration and proliferation

Effect of silencing PARG in human colon carcinoma LoVo cells on the ability of HUVEC migration and proliferation

Novel isothiacalothrixin B analogues exhibit cytotoxic activity on human colon cancer cells in vitro by inducing irreversible DNA damage

The Polymerization Agent, 2-Methyl-4′-(methylthio)-2-morpholinopropiophenone Induces Caspases-3/7 in Human Blood Mononuclear Cells <i>in Vitro</i>

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