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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.

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. [ABSTRACT FROM AUTHOR]

Ricin was encapsulated in various charged liposomes having 5mol% PEG of different chain length on the surface. The cytotoxicity of ricin entrapped in these liposomal formulations was examined in human epidermoid carcinoma (KB) cells with a view to develop an optimum delivery system for ricin in vivo. It was observed that the cytotoxicity of ricin entrapped in various charged liposomes was significantly dependent on the surface charge as well as chain length of PEG. The maximum cytotoxicity of ricin was observed when it was delivered through negatively charged liposomes having 5 mol% PEG-2000 on the surface. Monensin enhances the cytotoxicity of ricin entrapped in various charged liposomes depending on the surface charge. Maximum potentiation of cytotoxicity of ricin was observed when it was delivered through negatively charged liposomes having 5 mol% PEG-2000 on the surface. Studies on the kinetics of inhibition of protein synthesis by ricin revealed that the lag period of inhibition of protein synthesis is significantly lengthened following its delivery through various charged liposomes. Monensin significantly reduced the lag period of action of ricin. It was also observed that the efficacies of monensin on the enhancement of cytotoxicity of ricin entrapped in various charged PEG-liposomes were highly related to their amount of cell association. The current study has demonstrated that by suitable adjustment of charge, density, and chain length of PEG on the surface of liposomes it would be possible to direct liposomal ricin to human tumor cells for their selective elimination in combination with monensin. [ABSTRACT FROM AUTHOR]

Abstract: Ricin was encapsulated into various sterically stabilized liposomes having different density of folate on the surface and the cytotoxicity of ricin in these liposomes was examined in KB cells. The effect of monensin in free and various sterically stabilized liposomal forms having different density of folate on the surface on the enhancement of cytotoxicity of ricin entrapped in these liposomes was also examined. It was observed that liposomal ricin having 0.5mol% folate–PEG on the surface exhibits maximum cytotoxicity (IC50 =1274ng/ml) in KB cells as compared to non-targeted liposomes (IC50 =3274ng/ml). Monensin either in free form (266.2-fold) or liposomal form (291.5-fold) enhances the cytotoxicity of this targeted liposomal ricin significantly. This enhancement of the cytotoxicity of ricin entrapped in folate-targeted liposomes is further enhanced to 557.7-fold by monensin when it was delivered through folate-targeted (0.5mol% folate–PEG) liposomes. The present study has clearly demonstrated that ricin entrapped in folate-tagged-sterically stabilized liposomes in combination with monensin intercalated in folate-tagged-sterically stabilized liposomes may have potential application for the treatment of cancer cells over-expressing folate receptors on the cell surface. [Copyright &y& Elsevier]