Development of evaluation system for cancer chemopreventive agents based on DNA damage inhibition and gene expression

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Antioxidantg, such as vitamins and flavonoids contained in vegetables and fruits, have been believed to play the key role in cancer prevention. However, epidemiological studies demonstrated that b-carotene increased the incidences of lung cancer. We reported that b-carotene metabolites induced oxidative DNA damage. To establish the method to promote effective and Safe cancer chemoprevention, we investigated DNA damage and gene expression induced by chemopreventive agents as follows1. Phytic acid contained in cereals inhibited oxidative DNA damage in cultured cells. Phytic acid alone did not cause DNA damage. Thus, it can be a promising cancer chemopreventive agent.2. Although curcumin exhibits antitumor activity, carcinogenic properties have been reported. Curcumin treated with CYP2D6 induced DNA damage in the presence of Cu(II). Therefore, curcumin may exhibit carcinogenic potential through oxidative DNA damage by its metabolite.3. Whereas green tea catechins mediate cancer chemopreve … More ntive effects, epidemiological studies indicated positive relationship between green tea consumption and cancer. Catechins induced oxidative DNA damage in human cultured cells. Therefore, oxidative DNA damage may mediate carcinogenesis by catechins.4. Soy isoflavones are representative phytoestrogens that function as cancer chemopreventive agents. However, recent studies indicated that these isoflavones induced cancer of reproductive organs. Our findings suggest that oxidative DNA damage by isoflavone metabolites participates in tumor initiation and that cell proliferation by isoflavones themselves induces tumor promotion.5. we provided an extremely sensitive and specific method to quantify glutathione and other thiols using an electrochemical detector coupled to HPLC with a specially devised gold electrode.6. To examine protein expression by chemopreventive agents, we are performing proteome analysis using peptide mass fingerprinting. In estrogen-sensitive human breast cancer cells, estrogenic compounds increased the expression of VEFG-C, whereas the expression of flotillin-1, hnRNP L and lamin was decreased. Proteome analysis enables to evaluate the safety and effectiveness of chemopreventive agents. Less