Skin cancer, the most frequently diagnosed malignancy, with over 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 responses to antigens encountered in the skin and permits the growth of highly immunogenic skin cancers in laboratory animals. Although sunscreens reduce inflammation, they often lead to increased exposure. We have previously shown that crude extracts of Aloe barbadensis protect T-cell responses in mice when applied up to 24 hours following exposure to UV radiation. Aloe does this by virtue of at least two chemically and mechanistically different pharmacological systems one of which involves a cleavage oligosaccharide that downregulates the production of an immunosuppressive cytokine, Interleukin-10, by UV injured keratinocytes. In Phase I we established parameters and procedures for the controlled cleavage of the cytoprotective oligosaccharide from the native polysaccharide. In Phase II we will scale-up the process, develop real time quality control procedures and chemically characterize the biologically active oligosaccharide.
Oligosaccharides will be isolated by cellulose cleavage from native Aloe barbadensis gel. These will be suitable as therapeutic agents for use in a post sun car preparation designed to prevent injury by UV radiation to the skin immune system. Such a preparation has potential for the prevention of sun- induced skin cancer.
| Strickland, F M (2001) Immune regulation by polysaccharides: implications for skin cancer. J Photochem Photobiol B 63:132-40 |
