Skin cancer, the most frequently diagnosed malignancy with 800,000 new cases per year has a steadily rising incidence. The major environmental carcinogen, solar UV radiation, causes skin tumors in two ways: (i) as a mutagen for skin cells and (ii) as a suppressant of tumor surveillance. Exposure of skin to UV radiation suppresses T cell- mediated immune responses to antigens encountered in the skin and permits the growth of highly immunogenic skin cancers in laboratory animals. Although sunblocks reduce inflammation they often lead to increased exposure. Immune suppression by UV radiation is mediated by multiple complex, and interacting mechanisms. Clinical investigations suggest that these pathways are operant in patients with skin cancer. We have shown that crude extracts of Aloe barbadensis protect T cell responses in mice when applied up to 24 hours after exposure to UV radiation. Aloe does this by virtue by at least two chemically and mechanistically different pharmacologic systems one of which involves a cleavage oligosaccharide that downregulates the production of an immunosuppressive cytokine, Interleukin-10 by UV-injured keratinocytes. The commercial development of products that protect against UV-induced immunedamage as well as inflammation, is in its infancy. Commercially available preparations of Aloe barbadensis lack the ability to prevent UV-induced immune suppression. Currently, A. barbadensis extracts are produced and marketed as """"""""Aloe Vera"""""""", regulated under DHSEA. As a result, the industry is structurally incapable of producing materials to rigorous standards required to preserve the immune protective agents in Aloe. We will establish, Pangea Phytoceuticals, a company focused on plant oligosaccharides using scientific rather than """"""""folk lore"""""""" methods. This proposal encompasses the development of technologies for the production and analysis on a pilot-plant scale of Aloe cleavage immune- protective oligosaccharides. During Phase I, well characterized materials will be supplied to U.T.M.D. Anderson Cancer Center for studies on mechanism of action in vivo as well as in vitro.
Oligosaccharides will be isolated by cellulases cleavage from native Aloe barbadensis gel. These will be suitable as therapeutic agents for use in a post sun skin care preparation designed to prevent injury by UV radiation to the skin immune system. Such a preparation has potential for prevention of sun-induced skin cancer.
| Pelley, R P; Strickland, F M (2000) Plants, polysaccharides, and the treatment and prevention of neoplasia. Crit Rev Oncog 11:189-225 |
