Biological and antipathogenic activities of ribosome-inactivating proteins from Phytolacca dioica L

• Published in: Biochimica et biophysica acta Vol. 1860; no. 6; pp. 1256 - 1264
• Main Authors: Iglesias, Rosario, Citores, Lucía, Ragucci, Sara, Russo, Rosita, Di Maro, Antimo, Ferreras, José M.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.06.2016
• Subjects: Amino Acid Sequence; Antifungal; Antiviral; Apoptosis; Endonuclease; Endonucleases - metabolism; Molecular Sequence Data; Penicillium - drug effects; Phytolacca - chemistry; Polynucleotide:adenosine glycosylase; Protein Synthesis Inhibitors - pharmacology; Ribosome Inactivating Proteins - metabolism; Ribosome Inactivating Proteins - pharmacology; rRNA N-glycosylase; Antiviral; Antifungal; Endonuclease; Polynucleotide:adenosine glycosylase; rRNA N-glycosylase; Apoptosis
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/j.bbagen.2016.03.011

The species from the genus Phytolacca constitute one of the best sources of ribosome-inactivating proteins (RIPs) that have been used both in the therapy against virus and tumors and in the construction of transgenic plants resistant to virus, bacteria, fungi and insects. Here we investigate new activities of three representative RIPs from Phytolacca dioica (dioicin 2, PD-S2 and PD-L4). The three RIPs displayed, in addition to already reported activities, rRNA N-glycosylase activities against plant, bacterial and fungal ribosomes. Additionally dioicin 2 and PD-L4 displayed endonuclease activity on a supercoiled plasmid DNA, and dioicin 2 and PD-S2 arrested the growth of the fungus Penicillium digitatum. Furthermore, dioicin 2 induced caspase activation and apoptosis in cell cultures. The different activities of the RIPs from Phytolacca dioica may explain the antipathogenic properties attributed to these RIPs in plants and their antiviral and antitumoral effects. In spite of the similarity in their rRNA N-glycosylase and DNA polynucleotide:adenosine glycosylase activities, they differed in their activities against viral RNA, plasmid DNA, fungi and animal cultured cells. This suggests that the presence of isoforms might optimize the response of the plant against several types of pathogens. RIPs from Phytolacca can induce plant resistance or tumor cell death not only by means of ribosome inactivation but also by the activities found in this report. Furthermore, the induction of cell death by different mechanisms turns these RIPs into more useful tools for cancer treatment rendering the selection of RIP-resistant mutants impossible. [Display omitted] •RIPs from Phytolacca are active against animal, plant, fungal and bacterial ribosomes.•RIPs from Phytolacca display polynucleotide:adenosine glycosylase against DNA and RNA.•Some RIPs from Phytolacca display endonuclease (nicking) activity against plasmid DNA.•Some RIPs from Phytolacca display antifungal activity against Penicillium digitatum.•Dioicin 2 activates caspases 3/7 and induces apoptosis in COLO 320 and HeLa cells.