Dianthin and Its Potential in Targeted Tumor Therapies

Abstract

Dianthin enzymes belong to ribosome-inactivating proteins (RIPs) of type 1, i.e., they only consist of a catalytic domain and do not have a cell binding moiety. Dianthin-30 is very similar to saporin-S3 and saporin-S6, two RIPs often used to design targeted toxins for tumor therapy and already tested in some clinical trials. Nevertheless, dianthin enzymes also exhibit differences to saporin with regard to structure, efficacy, toxicity, immunogenicity and production by heterologous expression. Some of the distinctions might make dianthin more suitable for targeted tumor therapies than other RIPs. The present review provides an overview of the history of dianthin discovery and illuminates its structure, function and role in targeted toxins. It further discusses the option to increase the efficacy of dianthin by endosomal escape enhancers.

Mayahuelin, a Type I Ribosome Inactivating Protein: Characterization, Evolution, and Utilization in Phylogenetic Analyses of Agave

“…Although not as innocuous as in yeast cells, the IC 50 obtained for mayahuelin on a cell-free wheat germ extract was 10.43 nM (Figure 8). The IC 50 for inhibition of protein synthesis by RIPs varies according to the cell-free system used (Fuchs, 2019) and seems to be mediated by domains outside the catalytic site, which are highly variable among RIPs. For example, the IC 50 s for a RIP from Clerodendrum aculeatum (CA-SRI) are 0.008-and 0.8 nM in rabbit reticulcyte lysate and wheat germ systems, respectively, Kumar et al (1997).…”

“…For example, the IC 50 s for a RIP from Clerodendrum aculeatum (CA-SRI) are 0.008-and 0.8 nM in rabbit reticulcyte lysate and wheat germ systems, respectively, Kumar et al (1997). RIP IC 50 s in the wheat germ system cover more than three orders of magnitude, ranging from 0.2 nM, in the case of dodecandrin, to 800 nM for ricin A chain (Harley and Beevers, 1982;Reisbig and Bruland, 1983;Ferreras et al, 1993;Bonnes et al, 1994;Fuchs, 2019). In comparison, mayahuelin classifies as a RIP with medium capacity for protein inhibition in the wheat germ system.…”

Magnetic Nanoparticle-Based Dianthin Targeting for Controlled Drug Release Using the Endosomal Escape Enhancer SO1861

“…After recombinant expression in bacteria, Dia and DiaEGF were purified by Ni-NTA and chitin column affinity chromatography. Comprehensive analyses of the expression and purification of Dia and DiaEGF were carried in our previous studies [ 24 , 34 , 40 ] and will not be discussed in detail here. However, both RIPs, Dia and DiaEGF, appear as a single band in the SDS-PAGE ( Figure S2 ) at approximately 30 kDa and 36 kDa, respectively, and thus no degradation products were observable.…”

Ribosome-Inactivating Protein α-Momorcharin Derived from Edible Plant Momordica charantia Induces Inflammatory Responses by Activating the NF-kappaB and JNK Pathways

“…Thus, additional studies on the role of α-MMC in the immune system are needed in future. Given that α-MMC and other RIPs were observed to exert anti-tumor effects in various types of cancer cells [31,36,37,42], however, their inflammation inducing properties may hamper its potential use as a cancer therapeutic agent. Thus, the development of NF-κB and JNK inhibitors are certainly obvious candidates as combinatorial agents for α-MMC intoxication to deal with its proinflammatory effects.…”