A novel apoptotic pathway as defined by lectin cellular initiation

Gastman, Brian; Wang, Kent; Han, Jie; Zhu, Zhen; Huang, Xiaojun; Wang, Gui Qiang; Rabinowich, Hannah; Gorelik, Elieser

doi:10.1016/j.bbrc.2004.02.043

Cited by 35 publications

(29 citation statements)

References 23 publications

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“…Bars, 50 um. effect via mitochondria activation as it has been proposed for the lectins (14). Internalized carbohydrate-reactive IgM via its interaction with rafts may lead to modulation of cellular ceramide, which results in the induction of apoptosis (32).…”

Section: Discussionmentioning

confidence: 93%

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Reduction of Spontaneous Metastases through Induction of Carbohydrate Cross-Reactive Apoptotic Antibodies

Monzavi‐Karbassi

Artaud

Jousheghany

et al. 2005

The Journal of Immunology

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The selective targeting of tumor-associated carbohydrate Ags by the induction of serum Abs that trigger apoptosis of tumor cells as a means to reduce circulating tumor cells and micrometastases would be an advantage in cancer vaccine development. Some plant lectins like Griffonia simplicifolia lectin I and wheat germ agglutinin mediate the apoptosis of tumor cells. We investigated the possibility of using these lectins as templates to select peptide mimotopes of tumor-associated carbohydrate Ags as immunogens to generate cross-reactive Abs capable of mediating apoptosis of tumor cells. In this study, we show that immunization with a mimotope selected based on its reactivity with Griffonia simplicifolia lectin I and wheat germ agglutinin induced serum IgM Abs in mice that mediated the apoptosis of murine 4T1 and human MCF7 cell lines in vitro, paralleling the apoptotic activity of the lectins. Vaccine-induced anti-carbohydrate Abs reduced the outgrowth of micrometastases in the 4T1 spontaneous tumor model, significantly increasing survival time of tumor-bearing animals. This finding parallels suggestions that carbohydrate-reactive IgM with apoptotic activity may have merit in the adjuvant setting if the right carbohydrate-associated targets are identified.

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Section: Discussionmentioning

confidence: 93%

“…It is argued that the above-mentioned lectins trigger apoptosis via intracellular signaling following internalization (9,14). To better understand the mechanism of apoptosis by serum, we investigated the possibility of internalization of serum Abs.…”

Section: E-g Binding Of the Serum To 4t1 (E) Mcf7 (F) And Ark (G) mentioning

confidence: 99%

Reduction of Spontaneous Metastases through Induction of Carbohydrate Cross-Reactive Apoptotic Antibodies

Monzavi‐Karbassi

Artaud

Jousheghany

et al. 2005

The Journal of Immunology

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“…Apoptosis was analyzed by flow cytometry using FITC-conjugated Annexin V and propidium iodine (PI) as described [34]. In some experiments tumor cells were pretreated with different caspase inhibitors for 1-3 hrs prior to TRAIL treatment.…”

Section: Apoptosis Assaysmentioning

confidence: 99%

Multiple effects of TRAIL in human carcinoma cells: Induction of apoptosis, senescence, proliferation, and cytokine production

Levina

Marrangoni

DeMarco

et al. 2008

Experimental Cell Research

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TRAIL is a death ligand that induces apoptosis in malignant but not normal cells. Recently the ability of TRAIL to induce proliferation in apoptosis-resistant normal and malignant cells was reported. In this study, we analyzed TRAIL effects in apoptosis sensitive MCF7, OVCAR3 and H460 human tumor cell lines. TRAIL at low concentrations preferentially induced cell proliferation. At 100 ng/ ml apoptotic death was readily observed, however surviving cells acquired higher proliferative capacity. TRAIL stimulated production of several cytokines, IL-8, RANTES, MCP-1 and bFGF, and activation of caspases 1 and 8 was essential for this effect. Antibodies to IL-8, RANTES, and bFGF blocked TRAIL-induced cell proliferation and further stimulated apoptosis. For the first time, we report that high TRAIL concentrations induced cell senescence as determined by altered morphology and expression of several senescence markers: SA-β-gal, p21 Waf1/Cip1 , p16 INK4a , and HMGA. Caspase 9 inhibition protected TRAIL-treated cells from senescence, whereas inhibition of caspases 1 and 8 increased yield of SLP cells. In conclusion, in cultured human carcinoma cells, TRAIL therapy results in three functional outcomes, apoptosis, proliferation and senescence. TRAIL induced proapoptotic and prosurvival responses correlate with strength of signaling. TRAIL-induced cytokine production is responsible for its proliferative and prosurvival effects.

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“…The enormous developments that the possibility to inhibit, activate or exploit protein-carbohydrate interactions could 116 Studies indicated that GlcNAc-containing glycoconjugates were also involved in WGA-mediated cell death, and that the mechanism probably involved the mitochondrial pathway. Such valuable diagnostic and potential therapeutic applications highlight the need to gain further insights into lectinspecific ligand interactions and into the physiological processes that these associations initiate and/or regulate.…”

Section: Diagnostic and Therapeutic Applicationsmentioning

confidence: 99%

Lectins: Tools for the Molecular Understanding of the Glycocode

2005

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Recent progress in glycobiology has revealed that cell surface oligosaccharides play an essential role in recognition events. More precisely, these saccharides may be complexed by lectins, carbohydrate-binding proteins other than enzymes and antibodies, able to recognise sugars in a highly specific manner. The ubiquity of lectin-carbohydrate interactions opens enormous potential for their exploitation in BA (1993) and DPhil (1996) T h i s j o u r n a l i s © T h e R o y a l S o c i e t y o f C h e m i s t r y

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A novel apoptotic pathway as defined by lectin cellular initiation

Cited by 35 publications

References 23 publications

Reduction of Spontaneous Metastases through Induction of Carbohydrate Cross-Reactive Apoptotic Antibodies

Reduction of Spontaneous Metastases through Induction of Carbohydrate Cross-Reactive Apoptotic Antibodies

Multiple effects of TRAIL in human carcinoma cells: Induction of apoptosis, senescence, proliferation, and cytokine production

Lectins: Tools for the Molecular Understanding of the Glycocode

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