Sapovaccarin-S1 and -S2, Two Type I RIP Isoforms from the Seeds of Saponaria vaccaria L.

Schlaak, Louisa; Weise, Christoph; Kuropka, Benno; Weng, Alexander

doi:10.3390/toxins14070449

Cited by 3 publications

(3 citation statements)

References 43 publications

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“…Arginine at position 24 is not only preserved in dianthin-30 but also in saporin-S6, as previously shown [55]. In addition, the alignment of dianthin-30 with common type I and type II RIPs indicates that Arg24 is also conserved in sapovaccarin-S1, gelonin, gypsophilin-S, agrostin, bouganin, abrin A chain and ricin A chain [34,46,[68][69][70][71][72][73]. Thus, Arg24 is even found in type I RIPs like agrostin, which have an amino acid sequence that is unusual for the latter ones.…”

Section: Discussionsupporting

confidence: 62%

Mutational Analysis of RIP Type I Dianthin-30 Suggests a Role for Arg24 in Endocytosis

Schlaak,

Weise,

Kuropka

et al. 2024

Toxins

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Saponin-mediated endosomal escape is a mechanism that increases the cytotoxicity of type I ribosome-inactivating proteins (type I RIPs). In order to actualize their cytotoxicity, type I RIPs must be released into the cytosol after endocytosis. Without release from the endosomes, type I RIPs are largely degraded and cannot exert their cytotoxic effects. Certain triterpene saponins are able to induce the endosomal escape of these type I RIPs, thus increasing their cytotoxicity. However, the molecular mechanism underlying the endosomal escape enhancement of type I RIPs by triterpene saponins has not been fully elucidated. In this report, we investigate the involvement of the basic amino acid residues of dianthin-30, a type I RIP isolated from the plant Dianthus caryophyllus L., in endosomal escape enhancement using alanine scanning. Therefore, we designed 19 alanine mutants of dianthin-30. Each mutant was combined with SO1861, a triterpene saponin isolated from the roots of Saponaria officinalis L., and subjected to a cytotoxicity screening in Neuro-2A cells. Cytotoxic screening revealed that dianthin-30 mutants with lysine substitutions did not impair the endosomal escape enhancement. There was one particular mutant dianthin, Arg24Ala, that exhibited significantly reduced synergistic cytotoxicity in three mammalian cell lines. However, this reduction was not based on an altered interaction with SO1861. It was, rather, due to the impaired endocytosis of dianthin Arg24Ala into the cells.

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Section: Discussionsupporting

confidence: 62%

Mutational Analysis of RIP Type I Dianthin-30 Suggests a Role for Arg24 in Endocytosis

Schlaak,

Weise,

Kuropka

et al. 2024

Toxins

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“…Four examples of these type 1 RIPs are described in this Special Issue: the curcins from the euphorbiaceous Jatropha curcas L. [ 11 ], the sodins from the amaranthaceous Salsola soda L. [ 12 ], the sapovaccarins from the caryophyllaceous Vaccaria hispanica (Mill.) Rauschert (= Saponaria vaccaria L.) [ 13 ], and the PD-Ls from the phytolaccaceaous Phytolacca dioica L. [ 14 ].…”

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confidence: 99%

“…Schlaak et al isolated a new type 1 RIP from S. vaccaria seeds homologous to type 1 RIPs from other caryophyllaceous that, similar to dianthin 30 and saporin-S6, are used for the construction of immunotoxins [ 13 ]. Compared to other type 1 RIPs, they exhibited greater thermostability, suggesting that they would be optimal candidates for targeted cancer therapy.…”

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confidence: 99%

Biological Activities of Ribosome-Inactivating Proteins

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Ferreras

2023

Toxins

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Genotoxicity Assessment of Quinoin, a Ribosome Inactivating Protein from Quinoa Seeds, in the Teleost Danio rerio

Mottola,

Ragucci,

Carannante

et al. 2024

Front. Biosci. (Landmark Ed)

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Background: Ribosome inactivating proteins (RIPs) are N-glycosylases found in various plants that are able to specifically and irreversibly inhibit protein translation, thereby leading to cell death. Their cytotoxic properties have attracted attention in the medical field in the context of developing new anticancer therapies. Quinoin is a novel toxic enzyme obtained from quinoa seeds and classified as a type 1 RIP (Chenopodium quinoa Willd.). Recently, quinoin was found to be cytotoxic to normal fibroblasts and keratinocytes in vitro, as well as to several tumor cell lines. Methods: The aim of this study was to evaluate the in vitro and in vivo genotoxicity of quinoin in a zebrafish model. We evaluated its ability to induce DNA fragmentation, genomic instability, and reactive oxygen species (ROS) generation by means of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) reaction, randomly amplified polymorphic DNA (RAPD) Polymerase Chain Reaction (PCR) technique, and dichlorofluorescine (DCF) assay, respectively. Results: Quinoin was found to cause genomic damage in zebrafish, as shown by DNA fragmentation, polymorphic variations leading to genomic instability, and oxidative stress. Interestingly, longer quinoin treatment caused less damage than shorter treatments. Conclusions: This study demonstrated ROS-mediated genotoxicity of quinoin toward the zebrafish genome. The reduced damage observed after longer quinoin treatment could indicate the activation of detoxification mechanisms, activation of repair mechanisms, or the loss of protein activity due to enzymatic digestion. In order to clarify the genotoxic actions of quinoin, further investigations of the response pathways to DNA damage are needed. Overall, the ability of quinoin to cause breaks and instability in DNA, together with its clear cytotoxicity, make it an interesting candidate for the development of new drugs for cancer treatment.

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Sapovaccarin-S1 and -S2, Two Type I RIP Isoforms from the Seeds of Saponaria vaccaria L.

Cited by 3 publications

References 43 publications

Mutational Analysis of RIP Type I Dianthin-30 Suggests a Role for Arg24 in Endocytosis

Mutational Analysis of RIP Type I Dianthin-30 Suggests a Role for Arg24 in Endocytosis

Biological Activities of Ribosome-Inactivating Proteins

Genotoxicity Assessment of Quinoin, a Ribosome Inactivating Protein from Quinoa Seeds, in the Teleost Danio rerio

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