Modulation of MAPK Pathways by Food Phytochemicals: Risks and Benefi ts
Rapid and reliable methods of identifying cancer preventive compounds include screening of a wide range of natural or synthetic compounds that have biological and biochemical relevance to human carcinogenesis using in vitro assay systems. An alternative natural product chemistry approach that directs bioactive crude extracts involves activity-guiding separation, and then isolation and identifi cation
of the active principle, which is a powerful and effi cient technique to achieve the goal of compound identifi cation. Phorbol ester tumor promoters have been used in a great number of studies that attempted to identify novel candidates for cancer prevention, of which 12-O-tetradecanoylphorbol-13-acetate (TPA) was shown to activate oncogenic Epstein-Barr virus in several B-lymphoblastoid cell lines [1,2]. Our laboratory has conducted extensive screening tests of not only domestic vegetables and fruits , but also those from Southeast Asian countries, such as Thailand , Indonesia , and Malaysia . Interestingly, the in vitro antitumor promoting activities found in those subtropical plants were markedly higher than in plants typically found in Japan. Scientifi c reasons for the pronounced potentials of those plants remain to be elucidated. However, it is important to note that all plants have the potential to biosynthesize certain chemicals in response to environmental stress stimuli, such as ultraviolet (UV) exposure, invading insects, bacteria, and viruses (Figure 3.1). For example, plants biosynthesize polyphenols in order to scavenge free radicals generated from UV light exposure. Otherwise the proteins and DNA, which are critical for their survival, would become substantially damaged. Thus, it is not surprising that subtropical plants exposed to harsher types of stress produce greater numbers of biologically active phytochemicals of higher quality. As a result, we consider that vegetables and fruits commonly found in Southeast Asian countries are an attractive and promising source of cancer preventive compounds.