The 1,4 benzoquinone-featured 5-lipoxygenase inhibitor RF-Id induces apoptotic death through downregulation of IAPs in human glioblastoma cells

Zappavigna, Silvia; Scuotto, Maria; Cossu, Alessia Maria; Ingrosso, Diego; Rosa, Mario De; Schiraldi, Chiara; Filosa, Rosanna; Caraglia, Michele

doi:10.1186/s13046-016-0440-x

Cited by 19 publications

(16 citation statements)

References 35 publications

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“…Inhibitor of apoptosis proteins (IAPs) are anti-apoptotic proteins including cIAP1 (cellular inhibitor of apoptosis protein-1), cIAP2 (cellular inhibitor of apoptosis protein-2), XIAP and ML-IAP (melanoma inhibitor of apoptosis protein), and facilitate treatment resistance by inhibiting caspase activation [ 23 ]. XIAP degradation was induced and the NF-κB pathway was inhibited by 3-((decahydronaphthalen-6-yl)methyl)-2,5-dihydroxycyclohexa-2,5-diene-1,4-dione (RF-Id), which led to the cleavage of caspases 8, 9, 3, and 7, and blocked c-IAP2/XIAP interaction in in human glioblastoma U87MG and LN229 cells in vitro [ 24 ]. The caspase-dependent apoptosis in glioblastoma cells can be induced by RF-Id by inhibiting IAP family proteins and the NF-κB pathway.…”

Section: Discussionmentioning

confidence: 99%

Phenethyl Isothiocyanate Inhibits In Vivo Growth of Xenograft Tumors of Human Glioblastoma Cells

et al. 2018

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Phenethyl isothiocyanate (PEITC) from cruciferous vegetables can inhibit the growth of various human cancer cells. In previous studies, we determined that PEITC inhibited the in vitro growth of human glioblastoma GBM 8401 cells by inducing apoptosis, inhibiting migration and invasion, and altering gene expression. Nevertheless, there are no further in vivo reports disclosing whether PEITC can suppress the growth of glioblastoma. Therefore, in this study we investigate the anti-tumor effects of PEITC in a xenograft model of glioblastoma in nude mice. Thirty nude mice were inoculated subcutaneously with GBM 8401 cells. Mice with one palpable tumor were divided randomly into three groups: control, PEITC-10, and PEITC-20 groups treated with 0.1% dimethyl sulfoxide (DMSO), and 10 and 20 μmole PEITC/100 μL PBS daily by oral gavage, respectively. PEITC significantly decreased tumor weights and volumes of GBM 8401 cells in mice, but did not affect the total body weights of mice. PEITC diminished the levels of anti-apoptotic proteins MCL-1 (myeloid cell leukemia 1) and XIAP (X-linked inhibitor of apoptosis protein) in GBM 8401 cells. PEITC enhanced the levels of caspase-3 and Bax in GBM 8401 cells. The growth of glioblastoma can be suppressed by the biological properties of PEITC in vivo. These effects might support further investigations into the potential use of PEITC as an anticancer drug for glioblastoma.

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Section: Discussionmentioning

confidence: 99%

Phenethyl Isothiocyanate Inhibits In Vivo Growth of Xenograft Tumors of Human Glioblastoma Cells

et al. 2018

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“…Inhibition of IAPs suppresses proliferation and induces apoptosis in various tumor cells 23 - 25 . Second mitochondria-derived activator of caspases (SMAC) mimetics, which are designed based on the IAP-Binding Motif (IBM) of the potent endogenous antagonist of the IAPs, have been demonstrated to induce death in a subset of cancer cells in a caspase-8- and TNFα-dependent manner.…”

Section: Introductionmentioning

confidence: 99%

XIAP Limits Autophagic Degradation of Sox2 and Is A Therapeutic Target in Nasopharyngeal Carcinoma Stem Cells

Ji¹,

Yu²,

Li³

et al. 2018

Theranostics

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Rationale: Nasopharyngeal carcinoma (NPC) is the most frequent head and neck tumor in South China. The presence of cancer stem cells (CSCs) in NPC contributes to tumor maintenance and therapeutic resistance, while the ability of CSCs to escape from the apoptosis pathway may render them the resistant property to the therapies. Inhibitor of apoptosis proteins family proteins (IAPs), which are overexpressed in nasopharyngeal carcinoma stem cells, may play an important role in maintaining nasopharyngeal cancer stem cell properties. Here, we develop a novel CSC-targeting strategy to treat NPC through inhibiting IAPs.Methods: Human NPC S-18 and S-26 cell lines were used as the model system in vitro and in vivo. Fluorescence activated cell sorting (FACS) assay was used to detect nasopharyngeal SP cells and CD44+ cells. The characteristics of CSCs were defined by sphere suspension culture, colony formation assay and cell migration. The role of XIAP on the regulation of Sox2 protein stability and ERK1-mediated phosphorylation of Sox2 signaling pathway were analyzed using immunoblotting, immunoprecipitation, immunofluorescence, phosphorylation mass spectrometry, siRNA silencing and plasmid overexpression. The correlation between XIAP and Sox2 in NPC biopsies and their role in prognosis was performed by immunohistochemistry. APG-1387 or chemotherapies-induced cell death and apoptosis in S-18 and S-26 were determined by WST, immunoblotting and flow cytometry assay.Results: IAPs, especially X chromosome-linked IAP (XIAP), were elevated in CSCs of NPC, and these proteins were critically involved in the maintenance of CSCs properties by enhancing the stability of Sox2. Mechanistically, ERK1 kinase promoted autophagic degradation of Sox2 via phosphorylation of Sox2 at Ser251 and further SUMOylation of Sox2 at Lys245 in non-CSCs. However, XIAP blocked autophagic degradation of Sox2 by inhibiting ERK1 activation in CSCs. Additionally, XIAP was positively correlated with Sox2 expression in NPC tissues, which were associated with NPC progression. Finally, we discovered that a novel antagonist of IAPs, APG-1387, exerted antitumor effect on CSCs. Also, the combination of APG-1387 with CDDP /5-FU has a synergistic effect on NPC.Conclusion: Our study highlights the importance of IAPs in the maintenance of CSCs in NPC. Thus, XIAP is a promising therapeutic target in CSCs and suggests that NPC patients may benefit from a combination treatment of APG-1387 with conventional chemotherapy.

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“…Treatment of HQ for 24 h did not induce the cell death of A431 cells ( Figure 1 B), whereas, 12.5 μM HQ induced dramatic death of A431 cells at 48 ( Figure 1 C) and 72 h ( Figure 1 D) in a dose-dependent manner. Similarly to HQ, BQ belongs to a quinone group and has been demonstrated to exhibit anti-cancer activity [ 23 , 24 ]. Therefore, we compared the anti-cancer activity of HQ on A431 cells with that of BQ.…”

Section: Resultsmentioning

confidence: 99%

Hydroquinone Exhibits In Vitro and In Vivo Anti-Cancer Activity in Cancer Cells and Mice

Byeon

Lee

et al. 2018

IJMS

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Hydroquinone (HQ, 1,4-benzenediol) is a hydroxylated benzene metabolite with various biological activities, including anti-oxidative, neuroprotective, immunomodulatory, and anti-inflammatory functions. However, the anti-cancer activity of HQ is not well understood. In this study, the in vitro and in vivo anti-cancer activity of HQ was investigated in various cancer cells and tumor-bearing mouse models. HQ significantly induced the death of A431, SYF, B16F10, and MDA-MB-231 cells and also showed a synergistic effect on A431 cell death with other anti-cancer agents, such as adenosine-2′,3′-dialdehyde and buthionine sulfoximine. In addition, HQ suppressed angiogenesis in fertilized chicken embryos. Moreover, HQ prevented lung metastasis of melanoma cells in mice in a dose-dependent manner without toxicity and adverse effects. HQ (10 mg/kg) also suppressed the generation of colon and reduced the thickness of colon tissues in azoxymethane/dextran sodium sulfate-injected mice. This study strongly suggests that HQ possesses in vitro and in vivo anti-cancer activity and provides evidence that HQ could be developed as an effective and safe anti-cancer drug.

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The 1,4 benzoquinone-featured 5-lipoxygenase inhibitor RF-Id induces apoptotic death through downregulation of IAPs in human glioblastoma cells

Cited by 19 publications

References 35 publications

Phenethyl Isothiocyanate Inhibits In Vivo Growth of Xenograft Tumors of Human Glioblastoma Cells

Phenethyl Isothiocyanate Inhibits In Vivo Growth of Xenograft Tumors of Human Glioblastoma Cells

XIAP Limits Autophagic Degradation of Sox2 and Is A Therapeutic Target in Nasopharyngeal Carcinoma Stem Cells

Hydroquinone Exhibits In Vitro and In Vivo Anti-Cancer Activity in Cancer Cells and Mice

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