TPEN Induces Apoptosis Independently of Zinc Chelator Activity in a Model of Acute Lymphoblastic Leukemia and<i>Ex Vivo</i>Acute Leukemia Cells through Oxidative Stress and Mitochondria Caspase-3- and AIF-Dependent Pathways

Mendivil-Perez, Miguel; Vélez-Pardo, Carlos; Jiménez-Del-Río, Marlene

doi:10.1155/2012/313275

Cited by 59 publications

(53 citation statements)

References 64 publications

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“…AIF protein, which is located in the mitochondrial intermembrane space, exhibits apoptosis-inducing activity (34). In response to apoptotic stimuli, AIF molecules are released from the mitochondria into the cytoplasm followed by translocation to the nucleus and subsequent integration with chromosomal DNA, which leads to chromosome condensation and DNA breakage into large fragments (~50 kB) (35).…”

Section: Discussionmentioning

confidence: 99%

Xanthohumol inhibits proliferation of laryngeal squamous cell carcinoma

Wang

Yin

et al. 2016

Oncology Letters

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Abstract. Xanthohumol is a flavonoid compound that exhibits antioxidant and anticancer effects, and is used to treat atherosclerosis. The aim of the present study was to investigate the effect of xanthohumol on the cell proliferation of laryngeal squamous cell carcinoma and to understand the mechanism of its action. The effects of xanthohumol on the cell viability and apoptosis rate of laryngeal squamous cell carcinoma SCC4 cells were assessed by Annexin V-fluorescein isothiocyanate/propidium iodide staining. In addition, the expression levels of pro-apoptotic proteins, caspase-3, caspase-8, caspase-9, poly ADP ribose polymerase (PARP) p53 and apoptosis-inducing factor (AIF), as well as anti-apoptotic markers, B-cell lymphoma 2 (Bcl-2) and myeloid cell leukemia 1 (Mcl-1), were analyzed by western blotting. The results revealed that treatment with 40 µM xanthohumol significantly inhibited the proliferation of SCC4 cells. Furthermore, xanthohumol treatment (40 µM) induced SCC4 cell apoptosis, as indicated by the significant increase in activity and expression of caspase-3, caspase-8, caspase-9, PARP, p53 and AIF. By contrast, the protein expression of Bcl-2 and Mcl-1 was significantly decreased following treatment with 40 µM xanthohumol. Taken together, the results of the present study indicated that xanthohumol mediates growth suppression and apoptosis induction, which was mediated via the suppression of Bcl-2 and Mcl-1 and activation of PARP, p53 and AIF signaling pathways. Therefore, future studies that investigate xanthohumol as a potential therapeutic agent for laryngeal squamous cell carcinoma are required.

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Section: Discussionmentioning

confidence: 99%

Xanthohumol inhibits proliferation of laryngeal squamous cell carcinoma

Wang

Yin

et al. 2016

Oncology Letters

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“…7). TPEN, a known cytotoxic compound (38)(39)(40), was used as a positive control and showed toxicity at concentrations of Ͼ3.75 M, in agreement with previous findings (38,39). Most cyclic peptomers were not cytotoxic to HeLa cells, except for EpD-4=N, which showed toxicity at concentrations of Ͼ102 M. In addition, EpD-1N-treated cells displayed low absorbance in the MTT [3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide] assay at all concentrations, for reasons that are unclear but may reflect the compound's physical properties under these conditions.…”

Section: Development and Use Of An Nf-b-gfp Stable Cell Line For Idenmentioning

confidence: 99%

Synthetic Cyclic Peptomers as Type III Secretion System Inhibitors

Lam

Schwochert

Lao

et al. 2017

Antimicrob Agents Chemother

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Antibiotic-resistant bacteria are an emerging threat to global public health. New classes of antibiotics and tools for antimicrobial discovery are urgently needed. Type III secretion systems (T3SS), which are required by dozens of Gramnegative bacteria for virulence but largely absent from nonpathogenic bacteria, are promising virulence blocker targets. The ability of mammalian cells to recognize the presence of a functional T3SS and trigger NF-B activation provides a rapid and sensitive method for identifying chemical inhibitors of T3SS activity. In this study, we generated a HEK293 stable cell line expressing green fluorescent protein (GFP) driven by a promoter containing NF-B enhancer elements to serve as a readout of T3SS function. We identified a family of synthetic cyclic peptide-peptoid hybrid molecules (peptomers) that exhibited dose-dependent inhibition of T3SS effector secretion in Yersinia pseudotuberculosis and Pseudomonas aeruginosa without affecting bacterial growth or motility. Among these inhibitors, EpD-3=N, EpD-1,2N, EpD-1,3=N, EpD-1,2,3=N, and EpD-1,2,4=N exhibited strong inhibitory effects on translocation of the Yersinia YopM effector protein into mammalian cells (Ͼ40% translocation inhibition at 7.5 M) and showed no toxicity to mammalian cells at 240 M. In addition, EpD-3=N and EpD-1,2,4=N reduced the rounding of HeLa cells caused by the activity of Yersinia effector proteins that target the actin cytoskeleton. In summary, we have discovered a family of novel cyclic peptomers that inhibit the injectisome T3SS but not the flagellar T3SS.

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“…Zinc plays an important role in the regulation of apoptosis. It has been shown that the addition of Zn 2+ -chelators leads to apoptosisinduction in various hepatocytes, as well as in leukemia cells (33,34). Sequestering inhibitory Zn 2+ ions in inactive procaspase-3 generates active caspase-3, which subsequently triggers the downstream effector caspase-6 and induces apoptosis (33).…”

Section: +mentioning

confidence: 99%

Disulphide-reduced psoriasin is a human apoptosis-inducing broad-spectrum fungicide

Hein

Takahashi

Tsumori

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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The unexpected resistance of psoriasis lesions to fungal infections suggests local production of an antifungal factor. We purified Trichophyton rubrum-inhibiting activity from lesional psoriasis scale extracts and identified the Cys-reduced form of S100A7/psoriasin (redS100A7) as a principal antifungal factor. redS100A7 inhibits various filamentous fungi, including the mold Aspergillus fumigatus, but not Candida albicans. Antifungal activity was inhibited by Zn 2+, suggesting that redS100A7 interferes with fungal zinc homeostasis. Because S100A7-mutants lacking a single cysteine are no longer antifungals, we hypothesized that redS100A7 is acting as a Zn 2+ -chelator. Immunogold electron microscopy studies revealed that it penetrates fungal cells, implicating possible intracellular actions. In support with our hypothesis, the cell-penetrating Zn 2+ -chelator TPEN was found to function as a broad-spectrum antifungal. Ultrastructural analyses of redS100A7-treated T. rubrum revealed marked signs of apoptosis, suggesting that its mode of action is induction of programmed cell death. TUNEL, SYTOX-green analyses, and caspase-inhibition studies supported this for both T. rubrum and A. fumigatus. Whereas redS100A7 can be generated from oxidized S100A7 by action of thioredoxin or glutathione, elevated redS100A7 levels in fungal skin infection indicate induction of both S100A7 and its reducing agent in vivo. To investigate whether redS100A7 and TPEN are antifungals in vivo, we used a guinea pig tinea pedes model for fungal skin infections and a lethal mouse Aspergillus infection model for lung infection and found antifungal activity in both in vivo animal systems. Thus, selective fungal cellpenetrating Zn 2+ -chelators could be useful as an urgently needed novel antifungal therapeutic, which induces programmed cell death in numerous fungi.antifungal | innate immunity | epithelial defense | psoriasin | S100A7

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TPEN Induces Apoptosis Independently of Zinc Chelator Activity in a Model of Acute Lymphoblastic Leukemia andEx VivoAcute Leukemia Cells through Oxidative Stress and Mitochondria Caspase-3- and AIF-Dependent Pathways

Cited by 59 publications

References 64 publications

Xanthohumol inhibits proliferation of laryngeal squamous cell carcinoma

Xanthohumol inhibits proliferation of laryngeal squamous cell carcinoma

Synthetic Cyclic Peptomers as Type III Secretion System Inhibitors

Disulphide-reduced psoriasin is a human apoptosis-inducing broad-spectrum fungicide

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