Ricin: An Ancient Story for a Timeless Plant Toxin

Abstract

The castor plant (Ricinus communis L.) has been known since time immemorial in traditional medicine in the pharmacopeia of Mediterranean and eastern ancient cultures. Moreover, it is still used in folk medicine worldwide. Castor bean has been mainly recommended as anti-inflammatory, anthelmintic, anti-bacterial, laxative, abortifacient, for wounds, ulcers, and many other indications. Many cases of human intoxication occurred accidentally or voluntarily with the ingestion of castor seeds or derivatives. Ricinus toxicity depends on several molecules, among them the most important is ricin, a protein belonging to the family of ribosome-inactivating proteins. Ricin is the most studied of this category of proteins and it is also known to the general public, having been used for several biocrimes. This manuscript intends to give the reader an overview of ricin, focusing on the historical path to the current knowledge on this protein. The main steps of ricin research are here reported, with particular regard to its enzymatic activity, structure, and cytotoxicity. Moreover, we discuss ricin toxicity for animals and humans, as well as the relation between bioterrorism and ricin and its impact on environmental toxicity. Ricin has also been used to develop immunotoxins for the elimination of unwanted cells, mainly cancer cells; some of these immunoconjugates gave promising results in clinical trials but also showed critical limitation.

A double safety lock tumor-specific device for suicide gene therapy in breast cancer

“…In contrast, little or no effect was observed for HFF-1 cells, which are the most representative cell type in connective tissue[63] at all concentrations of the therapeutic device tested. This cytotoxic effect for pDhMUC1-ricin is in agreement with the expected toxic effects of ricin[64], thus suggesting the expression of functional and active ricin. Despite lacking CC50 data in MCF-7 cells, according to the literature, the CC50 for monkey kidney Vero cells incubated for 20 h with ricin is 7.6x10 -3 nM[65], which contrasts with value of 0.67 pM for HeLa cells[66] and 0.1 nM when myeloid U937 cells when incubated for 12 h[67], thus showing that ricin cytotoxicity depends on the cell line, probably due to the different composition of glycoproteins on the cellular surface and the internalization pathway.…”

Biofuel Production with Castor Bean: A Win–Win Strategy for Marginal Land

“…Castor bean has been used for a very long time and is one of the oldest commercial products [107], known in the traditional medicine of ancient Mediterranean and Asian cultures [108], being still used in traditional medicine worldwide (e.g., Chinese and Ayurveda) [21,108]. Long before "biobased" became a catchphrase, CB oil-derived products were used for centuries (e.g., in ancient Egypt lamps) [21,109].…”

Immunotoxins: Targeted Toxin Delivery for Cancer Therapy

“…Ricin can enter the target cells by endocytosis, then the two domains of ricin are reduced in endosomal vesicles; the domain A is transferred to the cytoplasm, which inactivates the ribosome by removing the base of G4323 in 28S rRNA of the ribosome, permanently inhibits cellular protein synthesis, and leads to cell death. 85 The deglycosylated A-chain of ricin (dgA) was also used to construct immunotoxins with a slower clearance rate. Since it is not easy to express functional ricin in Escherichia coli, ricin-based immunotoxins were constructed by chemically conjugating the ricin or dgA prepared by reduction to a targeting portion.…”

“…Since it is not easy to express functional ricin in Escherichia coli, ricin-based immunotoxins were constructed by chemically conjugating the ricin or dgA prepared by reduction to a targeting portion. 85…”