The Cytotoxicity of Elderberry Ribosome-Inactivating Proteins Is Not Solely Determined by Their Protein Translation Inhibition Activity

Abstract

Although the protein translation inhibition activity of ribosome inactivating proteins (RIPs) is well documented, little is known about the contribution of the lectin chain to the biological activity of these proteins. In this study, we compared the in vitro and intracellular activity of several S. nigra (elderberry) RIPs and non-RIP lectins. Our data demonstrate that RIPs from elderberry are much more toxic to HeLa cells than to primary fibroblasts. Differences in the cytotoxicity between the elderberry proteins correlated with differences in glycan specificity of their lectin domain, cellular uptake efficiency and intracellular destination. Despite the fact that the bulk of the RIPs accumulated in the lysosomes and partly in the Golgi apparatus, we could demonstrate effective inhibition of protein synthesis in cellula. As we also observed cytotoxicity for non-RIP lectins, it is clear that the lectin chain triggers additional pathways heralding cell death. Our data suggest that one of these pathways involves the induction of autophagy.

A Review of the Antiviral Properties of Black Elder (Sambucus nigraL.) Products

“…SNA‐V shows high homology to the Neu5Acα2,6Gal‐specific S. nigra bark lectin SNA‐I (van Damme et al, ) and may display antiviral properties (Vandenbussche et al, ). More specifically, SNA‐IV interacts with SAα2,6Gals similarly to S. nigra bark lectins, and SNA‐V with Gal and NAcGal residues, indicating competitive inhibition of pathogens, which utilize these galactose residues, as is seen with bark SNAs (van Damme et al, ; Shang et al, ). The extent of this potential inhibition is unknown, but it is unlikely to be the only antiviral mechanism in the plant, as S. nigra flowers have not been shown to contain these SNAs, yet have shown antiviral activity, as discussed in the Antiviral Properties section of this review.…”

“…The fruit contains a small concentration of an RIP with slight cytotoxic effects, SNA‐V, which is found in higher concentrations in the unripe fruit (Citores et al, ; Tejero et al, ). This is one of multiple RIPs that may harbor slight toxicity (van Damme et al, ; de Benito et al, ; Tejero et al, ; Shang et al, ). Thoroughly cooking the fruit (or boiling the juice) before use, however, should denature such proteins; while this has not yet been experimentally demonstrated with S. nigra RIPs, a study on S. ebulus berries found that heating the fruit sufficiently inhibited toxic effects from a lectin, which shows high homology to the S. nigra RIP Sam n1 (Jimenez et al, ).…”

Plant Lectins Targeting O-Glycans at the Cell Surface as Tools for Cancer Diagnosis, Prognosis and Therapy

“…Autophagy was also incriminated as a toxic effect of T/Tn-lectins on cancer cells [146]. In addition, the mechanism(s) underlying the cytotoxicity of T/Tn-specific lectins belonging to the type 2 Ribosome-Inactivation Proteins (RIPs), e.g., ricin, abrin and the mistletoe ( Viscum album ) lectins, partly differ from that of hololectins by the occurrence of a toxic A-chain acting as a potent protein biosynthesis inhibitor, which inhibits the ribosomal protein biosynthesis by depurinating the adenine base at position 2543 of the rRNA 28S [147].…”

Penapisan Senyawa Hemagglutinin dari Makroalga Asal Pantai Binuangeun, Banten, Indonesia

“…Lektin S.nigra yang secara spesifik mengenali galaktosa, N-acetylgalaktosamin (GalNac) tersebut dilaporkan juga mampu mengenali antigen Tn carcinoma (Maveyraud et al, 2009). Lebih lanjut, Shang et al (2015) melaporkan bahwa lektin dari S. nigra mampu memicu kematian sel HeLa melalui jalur tambahan ribosom inactivating proteins (RIPs), protein yang menghambat translasi pada ribosom.…”