Frontiers in Pharmacology | 2021
Editorial: Toxic Plant Proteins as Experimental Drugs for Human Pathologies
Abstract
Since the ancient times, plants extracts have been largely used in traditional and folk medicine (Polito et al., 2016a). Some of these medicinal plants are very toxic and their toxicity is often due to the presence of toxic proteins. Among plant toxins, the most known are ribosome-inactivating proteins (RIPs), a family of enzymes widely spread in the plant kingdom, especially in angiosperms, but also present in some fungal and bacterial species (Bolognesi et al., 2016; Polito et al., 2019). RIPs are monomeric (type 1) or dimeric (type 2) proteins depending on the absence or presence of a lectin B-chain linked to the enzymatic A-chain, respectively, being the type 2 RIPs much more toxic for cells. RIP activity was firstly identified as rRNA N-glycosylase. These enzymes were found to remove one specific adenine residue inside the GAGA sequence of the universally conserved sarcin-ricin loop (SRL) of the large rRNA subunit, thus irreversibly damaging ribosomes and causing the arrest of protein synthesis. Afterward, RIPs were also found to be able to deadenylate other substrates, such as genomic DNA, mRNA, tRNA, poly(A) and viral nucleic acids. After linking to appropriate carriers, such as antibodies (immunotoxins), RIPs have been used in experimental therapies to eliminate unwanted cells responsible of pathological conditions with promising results (Polito et al., 2016b). As RIPs have different intracellular substrates and they are able to elicit more than one cell death pathway (Polito et al., 2009; Polito et al., 2016c), they are potential payloads suitable for targeted cancer treatment. Moreover, no drug resistance is reported against RIPs and indeed these molecules were found to be active against cells that had developed multidrug resistance (Dinota et al., 1990). These characteristics make RIPs pharmacologically more attractive than conventional chemotherapy, in which one of the biggest problems is the selection of resistant cells. The collection of scientific articles composing this Research Topic highlights the progress in the understanding of cell damage mechanisms induced by plant toxins, thus underlying their potential anticancer activity. Moreover, this Research Topic provides an update of the correlations between molecular damages induced by RIPs and the triggering of different cell death pathways. The type 2 Riproximin, purified from Ximenia americana, has demonstrated specific antiproliferative activity in pancreatic ductal adenocarcinoma cells. Riproximin effects were evaluated in a nude rat model bearing pancreatic cancer cells by human and rat origins, miming both primary and metastatic tumor growth. Gene expression studies showed that Riproximin down-regulated genes involved in cancer progression (Sagini et al.). Stenodactylin is a highly toxic type 2 RIP purified from the caudex of Adenia stenodactyla. The anti-tumor effects of stenodactylin were demonstrated on acute myeloid leukemia cells. Genomewide gene expression microarray analysis revealed early changes in the expression of genes involved Edited and reviewed by: Salvatore Salomone, University of Catania, Italy