Analysis of Inhibitory Activity of Ricin Extracted from Ricinus Communis on Human Cancer Cell Lines and testing its activity on HIV receptor CD4 using Insilico analysis

Author Name: *Pooja Vaishnav Balotra
Author Email: poojavaishnav.ias@gmail.com

Abstract

Castor (Ricinus communis L.) is one of the oldest cultivated oil crops in the world. The unique oil produced in castor seeds contains ricinoleic acid, an essential product that is widely used as a raw material in numerous commercial applications. Ricin one of the storage protein of the seed is an cytotoxin used in various medicinal preparations in low concentrations, whereas the same in high concentrations is highly hazardous. The purpose of the current work is to extract the ricin protein from the castor seeds and after through purification testing its activity on Cancer Cell lines. The work was also extended to perform the insilico study of the same. The structure of the protein was retrieved and the protein-protein docking was performed using Hex software. The literature survey was done to identify the proteins that are responsible for causing Cancer. The protein structures were retrieved and were used to test their docking efficacy with the ricin protein. Based upon the docking interactions the probability of using ricin as a treatment mode for cancer can be detected.

Keywords

Ricinus Communis, Ricinoleic Acid, Protein- Protein Docking

Introduction

The castor bean plant is a tropical perennial shrub that originated in Africa and India, but is now cultivated in many tropical and subtropical regions around the world. It can be self and cross-pollinated and worldwide studies reveal low genetic diversity among castor bean. Approximately 90% of the oil from castor bean seeds is composed of the unusual hydroxylated fatty acid ricinoleic acid. Because of the nearly uniform ricinoleic acid content of castor oil, and the unique chemical properties that this fatty acid confers to the oil, castor bean is a highly valued oilseed crop for lubricant, cosmetic, medical and specialty chemical applications. Castor bean has also been proposed as a potential source of biodiesel; the high oil content of its seeds and the ease with which it can be cultivated in unfavorable environments contribute to its appeal as a crop in tropical developing countries. It is believed that castor oil was first used as an ointment 4,000 years ago in Egypt, from where it spread to other parts of the world, including Greece and Rome, where it was used as a laxative 2,500 years ago. An important obstacle to widespread cultivation of castor bean is the high content of ricin, an extremely toxic protein in its seeds. Ricin is considered one of the deadliest natural poisons when administered intravenously or inhaled as fine particles in high concentration. It is very surprising to know that inspite of its hazardous nature ricin when used in mild concentrations has the property to fight against dreadful diseases like Cancer and HIV. Ricin was first isolated more than a century ago. It has been reportedly used as a weapon and attempts to use ricin as a specific immunotoxin for therapeutic purposes in different cancers have been reported. Its biochemical activity has been characterized as a type 2 ribosome-inactivating protein (RIP), composed of two subunits linked by a disulfide bond: a 32 kDa ricin toxin A (RTA) chain that harbors the ribosome-inactivating activity, and a 34 kDa ricin toxin B (RTB) chain, with a galactose-binding lectin domain. RTA is an N-glycosidase that depurinates adenine in a specific residue of the 28S ribosomal RNA. The RTB chain allows ricin to enter eukaryotic cells by binding to cell surface galactosides and subsequent endocytosis. Other RIPs are common in plants, although they are not toxic because they are usually monomeric and lack a lectin domain. These proteins constitute the type 1 RIPs. The objective of the paper was to demonstrate the anticancer activity of the ricin protein extracted from ricinus communis. To establish its activity cancer cell lines were used. The anticancer activity of ricin was further analyzed using Insilco tools and software by applying the docking principle.

Conclusion

From the above study of ricin and its inhibitory activity against cancer and HIV it can be stated that ricin had good anticancer activity upon the tested cancer cell lines as indicated by their Optical density values measured by spectrophotometer. Similarly the anti HIV action has been tested in insilico conditions using Protein interaction studies or docking analysis. The HIV receptor selected here is the CD4 receptor protein to which the ricin is docked using Argus lab. The target site upon the CD4 was selected based on the antigen city and disorderness as analysed from PVS and RONN. The docking results indicate that the interaction between the two proteins was acceptable as the docking energy released was -5.451 kcal/mol. Further clinical studies can be undertaken to conform the activity of ricin in the treatment of HIV infections and control of cell proliferation in cancer conditions.

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