Wheat germ agglutinin-induced paraptosis-like cell death and protective autophagy is mediated by autophagy-linked FYVE inhibition

Tsai, Tsung-Yu; Wang, Hao Chen; Hung, Chun Hua; Lin, Peng; Lee, Yi San; Chen, Helen H.W.; Su, Wu Chou

doi:10.18632/oncotarget.20436

Cited by 14 publications

(2 citation statements)

References 49 publications

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“…Recently, there is evidence that WGA can kill via a completely different pathway. It has been demonstrated that WGA induces paraptosis-like cell death in cervical carcinoma cells (24). These different modes of killing, dependent on target cells, makes WGA an intriguing protein to study.…”

Section: Introductionmentioning

confidence: 99%

Wheat Germ Agglutinin as a Potential Therapeutic Agent for Leukemia

et al. 2019

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Dietary lectins are carbohydrate-binding proteins found in food sources. We used a panel of seven dietary lectins to analyze cytotoxicity against hematological cancers. Wheat germ agglutinin (WGA), even at low doses, demonstrated maximum toxicity toward acute myeloid leukemia (AML) cells. Using AML cell lines, we show time- and dose-dependent killing by WGA. We also show that low doses of WGA kills primary patient AML cells, irrespective of subtype, with no significant toxicity to normal cells. WGA caused AML cell agglutination, but failed to agglutinate RBC's at this dose. WGA, primarily, binds to N -acetyl-D-glucosamine (GlcNAc) and is also reported to interact with sialic-acid-containing glycoconjugates and oligosaccharides. After neuraminidase pre-treatment, which catalyzes the hydrolysis of terminal sialic acid residues, AML cells were less sensitive to WGA-induced cell death. AML cells were also not sensitive to succinyl-WGA, which does not react with sialic acid. Incubation with LEL lectin, which recognizes GlcNAc or SNA, which binds preferentially to sialic acid attached to terminal galactose in α-2,6 and to a lesser degree α-2,3 linkage, did not alter AML cell viability. These data indicate that WGA-induced AML cell death is dependent on both GlcNAc binding and interaction with sialic acids. We did not observe any in vitro or in vivo toxicity of WGA toward normal cells at the concentrations tested. Finally, low doses of WGA injection demonstrated significant in vivo toxicity toward AML cells, using xenograft mouse model. Thus, WGA is a potential candidate for leukemia therapy.

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Section: Introductionmentioning

confidence: 99%

Wheat Germ Agglutinin as a Potential Therapeutic Agent for Leukemia

et al. 2019

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“…Vacuolation, loss of cell architecture, and upregulation of the apoptosis-related proteins Bax and caspase-3 were observed. However, internucleosomal DNA fragmentation, apoptotic bodies, and related apoptotic phenotypes were not detected [50]. Meanwhile, WGA intake into pancreatic carcinoma cell lines caused chromatin condensation, nuclear fragmentation, and DNA release consistent with apoptosis [51].…”

Section: Cytotoxicitymentioning

confidence: 96%

Wheat Germ Agglutinin—From Toxicity to Biomedical Applications

Balčiūnaitė-Murzienė

Dzikaras

2021

Applied Sciences

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Wheat germ agglutinin is a hevein class N-Acetylglucosamine–binding protein with specific toxicity and biomedical potential. It is extractable from wheat germ—a low-value byproduct of the wheat industry—using well–established extraction methods based on salt precipitation and affinity chromatography. Due to its N-Acetylglucosamine affinity, wheat germ agglutinin exhibits antifungal properties as well as cytotoxic properties. Its anticancer properties have been demonstrated for various cancer cells, and toxicity mechanisms are well described. Wheat germ agglutinin has been demonstrated as a viable solution for various biomedical and therapeutic applications, such as chemotherapy, targeted drug delivery, antibiotic-resistant bacteria monitoring and elimination. This is performed mostly in conjunction with nanoparticles, liposomes, and other carrier mechanisms via surface functionalization. Combined with abundant wheat byproduct sources, wheat germ agglutinin has the potential to improve the biomedical field considerably.

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