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

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

Oncotarget (2017-12-07)
Tsung Lin Tsai, Hao Chen Wang, Chun Hua Hung, Peng Chan Lin, Yi San Lee, Helen H W Chen, Wu Chou Su
ABSTRACT

Wheat germ agglutinin (WGA) is a lectin that specifically binds cell surface glycoproteins and disrupts nuclear pore complex function through its interaction with POM121. Our data indicate WGA induces paraptosis-like cell death without caspase activation. We observed the main features of paraptosis, including cytoplasmic vacuolation, endoplasmic reticulum dilation and increased ER stress, and the unfolded protein response in WGA-treated cervical carcinoma cells. Conversion of microtubule-associated protein I light chain 3 (LC3-I) into LC3-II and punctuate formation suggestive of autophagy were observed in WGA-treated cells. WGA-induced autophagy antagonized paraptosis in HeLa and CaSKi cells, which expressed autophagy-linked FYVE (Alfy) protein, but not in SiHa cells that did not express Alfy. Alfy knockdown in HeLa cells induced paraptosis-like cell death. These data indicate that WGA-induced cell death occurs through paraptosis and that autophagy may exert a protective effect. WGA treatment and Alfy inhibition could be an effective therapeutic strategy for apoptosis-resistant cervical cancer cells.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-WDFY3 antibody produced in rabbit, affinity isolated antibody
Sigma-Aldrich
Lectin from Triticum vulgaris (wheat), suitable for cell culture, BioReagent, lyophilized powder
Sigma-Aldrich
Z-VAD-FMK, solid