Skin, the largest organ of the human body, is continuously exposed to environmental insults such as smoke, pollution, and ultraviolet (UV) irradiation. The thinning of the ozone layer, which is expected to progress for at least several decades, reduces a major barrier to the passage of ultraviolet-B radiation (UVB) through the atmosphere. UVB, that is, light whose wavelength is in the range between about 280 and about 320 nm, is the main cause of sunburn, tanning, aging of the skin, and skin cancer.
The non-melanoma skin cancers (NMSC), including basal-cell and squamous-cell carcinoma, are the most common types of cancer among Caucasian populations. The incidence of NMSC has increased worldwide over the last few decades. Increased recreational and occupational sunlight exposure is commonly regarded as one of the reasons for the higher incidence of cutaneous cancers. The increase in UVB exposure associated with the thinning of the ozone layer is another significant factor. Mortality from NMSC is low, but the estimated recurrence rate of about 50% after five years and the local invasiveness of this type of cancer result in high medical costs. Therefore, NMSC constitutes a substantial public health concern. (Reviewed in Holick and Kligman, editors: Biologic effects of light. Walter de Gruyter, Berlin and New York, 1992).
Photo-carcinogenesis results from a complex interplay of simultaneous and sequential biochemical events. These events, initiated by irradiation of an organism with UV light of an appropriate wavelength, include the formation of DNA photo-products, inaccuracies in DNA repair, mutation of proto-oncogenes and tumor suppressor genes, and UV-induced production of radical species which produce subsequent effects on existing mutations and independently induce further mutations. In addition, other epigenetic events such as immunological responses, antioxidant defenses, and dietary factors may influence the course of carcinogenesis. (Black, H. S., deGruijl, F. R., Forbes P. D., Cleaver, J. E., Ananthaswamy, H. N., deFabo, E. C., Ullrich, S. E., Tyrrell, R. M., Photocarcinogenesis: an overview. J. Photochem. Photobiol. B 40:1, 29-47, August, 1997).
The skin possesses an elaborate antioxidant defense system to deal with UV-induced oxidative stress. Excessive exposure to UV radiation, however, can overwhelm the cutaneous antioxidant capacity, leading to oxidative damage and ultimately to skin cancer and premature skin aging. Therefore, one strategy for photoprotection is to support the endogenous antioxidant system by induction or transdermal delivery of antioxidant enzymes or nonenzymatic antioxidants. Antioxidants such as glutathione, alpha-tocopherol, ascorbate and beta-carotene have been found to be very effective in photoprotection. Components of the antioxidant pathway have also been identified and applied to the skin of patients. Although skin treatments with single components of the antioxidant system such as vitamin E were successful against a wide variety of types of photodamage, they were not shown to affect the progression of UV-induced tumors. The most promising results were obtained in studies combining several compounds, which often resulted in synergy between the protective effects. (Steenvoorden D. D., van Henegouwen G. M., The use of endogenous antioxidants to improve photoprotection, J. Photochem. Photobiol., B 41:1-2, 1-10, November, 1997).
Epidemiological studies suggest that components of vegetables, particularly legumes, are beneficial in lowering the incidence rates of many types of cancer. For example, the rates of breast, colon and prostate cancer are significantly lower among the inhabitants of most countries of the Pacific Basin, but offspring of Pacific Basin natives who have migrated to the United States develop the common Western cancers at approximately the same rate as native Westerners. Such epidemiological studies suggest that dietary and other environmental factors, rather than genetic differences, contribute more significantly to the risk of susceptibility to these cancers. The high consumption of soybean products in Pacific Basin countries, such as Japan, implicates diet as one factor contributing to the relatively extremely low rates of cancer mortality in these countries. (E.g., Wu et al., Soy intake and risk of breast cancer in Asians and Asian Americans. Am. J. Clin. Nutr. 68: 6 Suppl., 1437S-1443S, December, 1998).
Soybeans are a rich source of isoflavones, which possess weak estrogenic activity. Genistein, the main soybean isoflavone, is a specific inhibitor of protein tyrosine kinases and of other enzymes involved in signal transduction. Genistein has been shown to suppress the growth of numerous cancer cells in vitro, and to protect animals in experimental carcinogenesis models from developing both hormone- and non-hormone related cancers. (Reviewed in A. R. Kennedy, Chemopreventive agents: Protease inhibitors, Pharmacology Theories 78 (3), 167-209), 1998 and in Messina et al., Soy intake and cancer risks: A review of the in vitro and in vivo data, Nutrition and Cancer 21 (2), 113-131, 1994).
Soybeans also contain a number of protease inhibitors such as BBI and STI. It is important to note that soy foods do not contain high concentrations of active STI and BBI, because these protease inhibitors block the action of trypsin and other enzymes needed for protein digestion. Although STI is denatured by cooking, heat alone does not inactivate BBI, and consumption of soy products containing high levels of these protease inhibitors leads to serious digestive problems, chronic deficiency in amino acid uptake, and cancer. Indeed, the Chinese did not serve soybeans as food until fermentation techniques were developed to destroy the anti-digestive properties of the soy foods (2nd century B.C.E.). During the production of soy foods today, pureed soybeans are soaked in an alkaline solution and then pressure-heated to 115εC in order to denature the protease inhibitors as much as possible.
Limtrakul et al. attempted to identify a safe level of soy proteins for nutritional consumption, which would be beneficial in the prevention of cancer. Skin tumors were chemically induced in mice, which were fed soy protein isolate (SPI) exclusively, and in mice which were fed SPI supplemented with soymilk proteins (SMP). It was reported that “the percentage of tumor-bearing mice and the volume of tumor tended to be lower in the mice on the SMP diet”. Life Sciences 1993, 53, 1591-1596. When defatted soybeans are treated first with alkaline, then with acid solution, SPI is the precipitate and SMP is the supernatant. The Limtrakul study shows the potential of soy proteins to affect skin cancer progression, when the proteins are orally consumed. However, it was also emphasized that higher levels of dietary intake of SMP would result in major health problems.
It is clear that a need exists for safe, efficacious and economical agents that prevent or reduce incidence of cancer, particularly for NMSC, which may be simply and conveniently administered. Further, economical and prophylactic compositions and methods for the reduction, prevention or inhibition of the progression of UV-induced cutaneous tumors are highly desirable. Since topical application is very simple and convenient, incorporating compositions that reduce skin cancer incidence into a skin-care product would be extremely advantageous. While sunscreens are known to reduce the damage resulting from UV exposure during the period of their application, there is a need for a skin care product that could also slow the progression of already-initiated photocarcinogenic processes. It is an object of the invention to provide such a product.
USPTO Backgrounds
USPTO Backgrounds