Shiga toxins and apoptosis

Cherla, Rama P.; Lee, Sang-Yun; Tesh, Vernon L.

doi:10.1016/s0378-1097(03)00761-4

Cited by 100 publications

(74 citation statements)

References 46 publications

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“…Cell lines such as T84 or HT29 have been in use for decades and may have therefore acquired genetic and epigenetic alterations not found in the primary tumors. Thus, it seems that apoptosis induction by Shiga toxin strongly depends on the cell type, and may rely on different mechanisms (45).…”

Section: Discussionmentioning

confidence: 99%

Human colorectal tumors and metastases express Gb3 and can be targeted by an intestinal pathogen-based delivery tool

Falguières

Maak

Weyhern

et al. 2008

Molecular Cancer Therapeutics

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The targeting of solid tumors requires delivery tools that resist intracellular and extracellular inactivation, and that are taken up specifically by tumor cells. We have shown previously that the recombinant nontoxic B-subunit of Shiga toxin (STxB) can serve as a delivery tool to target digestive tumors in animal models. The aim of this study was to expand these experiments to human colorectal cancer. Tissue samples of normal colon, benign adenomas, colorectal carcinomas, and liver metastases from 111 patients were obtained for the quantification of the expression of the cellular STxB receptor, the glycosphingolipid globotriaosyl ceramide (Gb 3 or CD77). We found that compared with normal tissue, the expression of Gb 3 was strongly increased in colorectal adenocarcinomas and their metastases, but not in benign adenomas. Short-term primary cultures were prepared from samples of 43 patients, and STxB uptake was studied by immunofluorescence microscopy. Of a given tumor sample, on average, 80% of the cells could visibly bind STxB, and upon incubation at 37°C, STxB was transported to the Golgi apparatus, following the retrograde route. This STxB-specific intracellular targeting allows the molecule to avoid recycling and degradation, and STxB could consequently be detected on tumor cells even 5 days after initial uptake. In conclusion, the targeting properties of STxB could be diverted for the delivery of contrast agents to human colorectal tumors and their metastases, whose early detection and specific targeting remains one of the principal challenges in oncology. [Mol Cancer Ther 2008;7(8):2498 -508]

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Section: Discussionmentioning

confidence: 99%

Human colorectal tumors and metastases express Gb3 and can be targeted by an intestinal pathogen-based delivery tool

Falguières

Maak

Weyhern

et al. 2008

Molecular Cancer Therapeutics

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“…In our study, B subunit causing DNA laddering was lower than A subunit. Similarly in this experiment, studying HeLa cell has suggested that toxin enzymatic activity is necessary to induce apoptosis through a mechanism completely independent of caspase activation (Cherla et al 2003). B subunit of Stx is supposed to be a convenient non-cytotoxic model ) of holotoxin internalization, and Stx A subunit lacks known trafficking motifs (Jackson et al 1999); the A subunit might also modify holotoxin transport via unknown motifs.…”

Section: Discussionmentioning

confidence: 81%

“…In different cell types, toxins may signal apoptosis via different mechanisms (Cherla et al 2003). Therefore, there are highly Stx-sensitive cells with a variant receptor fatty acid, which plays a key role in the kind of intracellular trafficking and sorting of the toxin to the cytosol (O'Loughlin and Robins-Browne 2001).…”

Section: Introductionmentioning

confidence: 99%

Study on induction of apoptosis on HeLa and Vero cells by recombinant shiga toxin and its subunits

2009

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Verotoxin (VT) or shiga toxin (Stx) produced by enterohemorrhagic Escherichia coli (EHEC) and Shigella dysenteriae is AB5 holotoxin with potent protein synthesis inhibitor. VT can induce both apoptosis and necrosis depending on the cell type, it has been shown that VT-induced apoptosis and cytotoxicity are distinct processes, and the A subunit can be necessary for apoptosis. In other words, the precise role of each subunit in apoptosis signaling has yet to be established. In this study, induction of apoptosis has been examined by using both recombinant A and B subunits, and recombinant Stx (rStx) with different doses in HeLa and Vero cells. For this purpose, the polymyxin B extract of constructs expressing A, B and AB5 recombinant proteins was used. Therefore, amounts greater than normally reported were used to induce desire effects on cell lines. The apoptotic effect of A and B subunits appear at higher doses than that of rStx. The highest apoptotic effect was observed for rStx at low concentration, compared to A and B subunits. A or B subunits separately cannot induce the signaling pathway stimulated by holotoxin though A subunit, does induce laddering pattern similar to holotoxin. We concluded that both subunits are important in complete death signaling pathway. Since different concentration of A and B subunits and rStx was required in different assay, therefore, it could be emphasized that cell death or even apoptosis caused by either of the subunits or holotoxin depends on sensitivity or specificity of the assay and cell types used.

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“…Numerous recent studies have shown Stx's trigger programmed cell death signaling cascades in intoxicated cells. The mechanisms of apoptosis induced by these toxins are emerging recently, and the data published to date suggest that the toxin may signal apoptosis in different cells types via different mechanisms (Cherla et al, 2003). From what was described above, it is possible to deduce that Shiga toxin may also affect other organs and that apoptotic signs could be considered as toxic cell injuries.…”

Section: Introductionmentioning

confidence: 97%

Excretion Products of Shigella dysenteriae and Apoptotic Cell Death on Chick Embryo Muscle Tissue

et al. 2007

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SUMMARY:The aim of this study was to evaluate the acute cell injury of excretion products present in culture filtrate from Shigella dysenteriae in both whole lower limb of chick embryo ex vivo and myoblasts cells developed in hanging-drop cultures in vitro. Three controls were defined: a) Tyrode's solution b) brain-heart broth infusion (CCC) and c) supernatant not toxigenic of E.coli O157:H7. Shigella dysenteriae were culture for 24 hours and the excretion products were obtained after centrifugation of the culture. After 1h of treatment, the morphologic changes in limbs treated with raw filtrate were evaluated through histopathological examination of sections stained with hematoxylin-eosin (H&E-stain) and Gomori's trichrome by image analysis techniques. Quantification of apoptotic cells was measured by an enzyme-linked immunoassay TUNEL. The morphological feature of apoptosis were evaluated in culture myoblasts. In contrast with controls, the longitudinal section on treated thigh of chick embryo limb-buds show atrophy muscle tissue, detachment of few fibers, 57,14% decrease in the number of cells, and loss of collagen substrate. Apoptotic index percent increase and mitotic index decrease in response to excretion products were observed, but were not significant. Membrane blebbing, vacuolation, small aggregates of chromatin around the nucleus and loss of cell adhesion were observed. Culture filtrate from Shigella dysenteriae produced cytotoxic effect on cell of muscle fibers with acute cell injuries suspected to be related to the apoptotic cell death.

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Shiga toxins and apoptosis

Cited by 100 publications

References 46 publications

Human colorectal tumors and metastases express Gb3 and can be targeted by an intestinal pathogen-based delivery tool

Human colorectal tumors and metastases express Gb3 and can be targeted by an intestinal pathogen-based delivery tool

Study on induction of apoptosis on HeLa and Vero cells by recombinant shiga toxin and its subunits

Excretion Products of Shigella dysenteriae and Apoptotic Cell Death on Chick Embryo Muscle Tissue

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