Retinoids and cancer prevention: crossing the line between food and drug

being different. We all know many people who stop and start smoking, drinking, and dieting regularly. Yet, we tend to think of diet modification as a long-term, holistic, “natural,” non-specific method of health maintenance. We all know people who eat herbs (such as St. John’s Wort and gingko biloba), nutrients (such as vitamin C and antioxidant complexes), and nutrition-based drugs for years in the hope that they will prevent disease. Yet, we think of chemoprevention as being harsh, effective, and narrowly focused on short-term treatments or prevention of cancer. This narrow focus may have been especially true for retinoid (vitamin A) research. Researchers made exciting and rapid progress in retinoid genetics, metabolism, and cell differentiation in the 1980s and 1990s.4 This progress occurred at the same time, but generally in different laboratories, as exciting and rapid developments in ascertaining the causes, consequences, and prevention of vitamin A deficiency. 5 The explosion in information was difficult to assimilate and use effectively. Retinoid research essentially split into two camps. “Retinoid” researchers, mostly working in the United States and Europe, investigated cellular mechanisms of differentiation, and cancer chemoprevention. “Vitamin A” researchers, mostly working in the developing countries, investigated the effects of dietary intervention and modification on vitamin A deficiency. There were Retinoid conferences and Vitamin A conferences (few scientists attended both). However, the lines between “diet” modification and “drug”-based chemoprevention are not so difficult to cross. The retinoid family of nutrients provides some of the most successful nutrient-based cancer chemopreventatives we have, and is used in some of the most successful diet modification programs. Research on diet modification programs using vitamin A have been summarized elsewhere.5 Retinoids as cancer chemopreventive agents are reviewed in this issue.6 Retinoids are powerful chemicals that regulate cell differentiation and proliferation. Cancer involves the disruption of normal cell differentiation, so it was obvious that retinoid status might influence a cell’s potential for malignant transformation. Early studies showed that vitamin A deficiency could lead to cancer in animals, and that retinoids could interfere with cancer initiation and progression in cell culture. 6,7 These exciting results were followed by many more studies, which are summarized in this interesting review.6