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.
Highlights
Wheat germ agglutinin (WGA) is lectin consisting of two identical subunits
WGA is suitable for targeted drug delivery because it binds to membrane-associated glycoproteins that are highly expressed on the surfaces of some cancer cells [4,5,6]
WGA induces cytoplasmic vacuolization and cell death in cervical carcinoma cells We performed MTT assay to assess the cytotoxicity of WGA in HeLa, SiHa, and CaSKi cervical carcinoma cell lines
Summary
Wheat germ agglutinin (WGA) is lectin consisting of two identical subunits. It inhibits export of nuclear RNA by the nuclear pore complex and protein shuttling through its interaction with POM121 [1,2,3]. WGA is suitable for targeted drug delivery because it binds to membrane-associated glycoproteins that are highly expressed on the surfaces of some cancer cells [4,5,6]. We previously demonstrated that WGA has a tumor-suppressive effect similar to that of nuclear signaling peptide-modified gold nanoparticles, which block nucleocytoplasmic transport [11]. The mechanisms underlying the anti-tumor activity of WGA have not been elucidated
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