Ageritin, a Ribotoxin from Poplar Mushroom (Agrocybe aegerita) with Defensive and Antiproliferative Activities

• Published in: ACS chemical biology Vol. 14; no. 6; pp. 1319 - 1327
• Main Authors: Citores, Lucía, Ragucci, Sara, Ferreras, José M, Di Maro, Antimo, Iglesias, Rosario
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 21.06.2019
• Subjects: Agrocybe - chemistry; Anti-Infective Agents - pharmacology; Cell Line, Tumor; Cell Proliferation - drug effects; Cytotoxins - pharmacology; Drug Screening Assays, Antitumor; Humans; Microbial Sensitivity Tests; Micrococcus - drug effects; Ribonucleases - isolation & purification; Ribonucleases - pharmacology; Tobacco Mosaic Virus - drug effects
• DOI: 10.1021/acschembio.9b00291
• ISSN: 1554-8929

Ribotoxins make up a group of extracellular rRNA endoribonucleases produced by ascomycetes that display cytotoxicity toward animal cells, having been proposed as insecticidal agents. Recently, the ribotoxin Ageritin has been isolated from the basidiomycetes Agrocybe aegerita (poplar mushroom), suggesting that ribotoxins are widely distributed among fungi. To gain insights into the protective properties of Ageritin against pathogens and its putative biotechnological applications, we have tested several biological activities of Ageritin, comparing them with those of the well-known ribotoxin α-sarcin, and we found that Ageritin displayed, in addition to the already reported activities, (i) antibacterial activity against Micrococcus lysodeikticus, (ii) activity against the tobacco mosaic virus RNA, (iii) endonuclease activity against a supercoiled plasmid, (iv) nuclease activity against genomic DNA, (v) cytotoxicity to COLO 320, HeLa, and Raji cells by promoting apoptosis, and (vi) antifungal activity against the green mold Penicillium digitatum. Therefore, Ageritin and α-sarcin can induce resistance not only to insects but also to viruses, bacteria, and fungi. The multiple biological activities of Ageritin could be exploited to improve resistance to different pathogens by engineering transgenic plants. Furthermore, the induction of cell death by different mechanisms turns these ribotoxins into useful tools for cancer therapy.