Potential Therapeutic Applications of Plant Toxin-ricin in Cancer: Challenges and Advances

Overview

Journal Tumour Biol

Publisher Sage Publications

Specialty Oncology

Date 2015 Sep 10

PMID 26349746

Citations 23

Authors

Nikhil Tyagi

Monika Tyagi

Manendra Pachauri

Prahlad C Ghosh

Affiliations

Soon will be listed here.

Abstract

Cancer is one of the most common devastating disease affecting millions of people per year worldwide. To fight against cancer, a number of natural plant compounds have been exploited by researchers to discover novel anti-cancer therapeutics with minimum or no side effects and plants have proved their usefulness in anti-cancer therapy in past few years. Ricin, a cytotoxic plant protein isolated from castor bean seeds, is a ribosome-inactivating protein which destroys the cells by inhibiting proteins synthesis. Ricin presents great potential as anti-cancer agent and exerts its anti-cancer activity by inducing apoptosis in cancer cells. In this review, we summarize the current information on anti-cancer properties of plant toxin ricin, its potential applications in cancer therapy, challenges associated with its use as therapeutic agent and the recent advances made to overcome these challenges. Nanotechnology could open the doors for quick development of ricin-based anti-cancer therapeutics. Conceivably, ricin may serve as a chemotherapeutic agent against cancer by utilizing nanocarriers for its targeted delivery to cancer cells.

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References

Olsnes S . The history of ricin, abrin and related toxins. Toxicon. 2004; 44(4):361-70. DOI: 10.1016/j.toxicon.2004.05.003. View

Watanabe Y, Osawa T . Effect of ricin or ricin A-chain encapsulated in anti-carcinoembryonic antigen (CEA) antibody-bearing liposomes on CEA-producing tumor cells. Chem Pharm Bull (Tokyo). 1987; 35(2):740-7. DOI: 10.1248/cpb.35.740. View

Blakey D, Skilleter D, Price R, Watson G, HART L, Newell D . Comparison of the pharmacokinetics and hepatotoxic effects of saporin and ricin A-chain immunotoxins on murine liver parenchymal cells. Cancer Res. 1988; 48(24 Pt 1):7072-8. View

MOSINGER M . [Necrosing or clastic effects of ricin on different organs and on experimental sarcomas]. C R Seances Soc Biol Fil. 1951; 145(5-6):412-5. View

Shkedy D, Singh N, Shemesh K, Amir A, Geiger T, Liefshitz B . Regulation of Elg1 activity by phosphorylation. Cell Cycle. 2015; 14(23):3689-97. PMC: 4825795. DOI: 10.1080/15384101.2015.1068475. View

Singh V, Sairam M, Bhargavi G, Akhras R . Hormonotoxins. Preparation and characterization of ovine luteinizing hormone-gelonin conjugate. J Biol Chem. 1989; 264(6):3089-95. View

Preijers F, Tax W, de Witte T, Janssen A, vd Heijden H, Vidal H . Relationship between internalization and cytotoxicity of ricin A-chain immunotoxins. Br J Haematol. 1988; 70(3):289-94. DOI: 10.1111/j.1365-2141.1988.tb02484.x. View

Gosselin M, Lee R . Folate receptor-targeted liposomes as vectors for therapeutic agents. Biotechnol Annu Rev. 2002; 8:103-31. DOI: 10.1016/s1387-2656(02)08006-7. View

Sha O, Yew D, Ng T, Yuan L, Kwong W . Different in vitro toxicities of structurally similar type I ribosome-inactivating proteins (RIPs). Toxicol In Vitro. 2010; 24(4):1176-82. DOI: 10.1016/j.tiv.2010.02.014. View

10.

Roberts L, Lamb F, Pappin D, Lord J . The primary sequence of Ricinus communis agglutinin. Comparison with ricin. J Biol Chem. 1985; 260(29):15682-6. View

11.

Press O, Vitetta E, Farr A, Hansen J, Martin P . Evaluation of ricin A-chain immunotoxins directed against human T cells. Cell Immunol. 1986; 102(1):10-20. DOI: 10.1016/0008-8749(86)90321-7. View

12.

Deshmukh S, Srivastava S, Bhardwaj A, Singh A, Tyagi N, Marimuthu S . Resistin and interleukin-6 exhibit racially-disparate expression in breast cancer patients, display molecular association and promote growth and aggressiveness of tumor cells through STAT3 activation. Oncotarget. 2015; 6(13):11231-41. PMC: 4484452. DOI: 10.18632/oncotarget.3591. View

13.

Richardson P, Westby M, Roberts L, Gould J, Colman A, Lord J . Recombinant proricin binds galactose but does not depurinate 28 S ribosomal RNA. FEBS Lett. 1989; 255(1):15-20. DOI: 10.1016/0014-5793(89)81052-x. View

14.

Liao P, Liu W, Li H, Gao H, Wang H, Li N . Morphological changes of ricin toxin-induced apoptosis in human cervical cancer cells. Toxicol Ind Health. 2011; 28(5):439-48. DOI: 10.1177/0748233711414608. View

15.

Peer D, Karp J, Hong S, Farokhzad O, Margalit R, Langer R . Nanocarriers as an emerging platform for cancer therapy. Nat Nanotechnol. 2008; 2(12):751-60. DOI: 10.1038/nnano.2007.387. View

16.

Srivastava S, Bhardwaj A, Arora S, Tyagi N, Singh A, Carter J . Interleukin-8 is a key mediator of FKBP51-induced melanoma growth, angiogenesis and metastasis. Br J Cancer. 2015; 112(11):1772-81. PMC: 4647250. DOI: 10.1038/bjc.2015.154. View

17.

Singh M, Griffin T, Salimi A, Micetich R, Atwal H . Potentiation of ricin A immunotoxin by monoclonal antibody targeted monensin containing small unilamellar vesicles. Cancer Lett. 1994; 84(1):15-21. DOI: 10.1016/0304-3835(94)90353-0. View

18.

Sandvig K, van Deurs B . Transport of protein toxins into cells: pathways used by ricin, cholera toxin and Shiga toxin. FEBS Lett. 2002; 529(1):49-53. DOI: 10.1016/s0014-5793(02)03182-4. View

19.

Griffiths G, Leek M, GEE D . The toxic plant proteins ricin and abrin induce apoptotic changes in mammalian lymphoid tissues and intestine. J Pathol. 1987; 151(3):221-9. DOI: 10.1002/path.1711510310. View

20.

Epler K, Padilla D, Phillips G, Crowder P, Castillo R, Wilkinson D . Delivery of ricin toxin a-chain by peptide-targeted mesoporous silica nanoparticle-supported lipid bilayers. Adv Healthc Mater. 2012; 1(3):348-53. PMC: 4119887. DOI: 10.1002/adhm.201200022. View