Seeking an effective, safe, inexpensive, natural product to prevent breast cancer in women is an exciting field in cancer research. A higher concentration of aromatic DNA adducts occur in normal breast tissues surrounding tumor in breast cancer patients than that in women without cancer. This indicates that environmental carcinogenic exposure is involved in breast cancer development. Most experts recognize that carcinogenic DNA adduct formation is the earliest critical step in carcinogenesis. The reduction of DNA adduct formation is, at least, a new avenue of monitoring cancer prevention at the initiation stage of carcinogenesis. Since the identification of carcinogenic exposure in human breast cancer is difficult because of unknown variables, it is difficult to study mechanisms of how a preventive agent influences human breast cancer development. 'Huggins' tumor model using dimethylbenz(a)anthracene (DMBA) in female SD rats closely mimics human breast cancer. In this proposal, we will use this tumor model to examine the preventive effect of Morinda citrifolia (Noni) fruits juice and how Noni fruits juice influences mammary tumor development. Noni is a common name of Morinda citrifolia, which has been used as a folk medicine by Polynesians for over 2,000 years. It is believed that Noni has a broad range of beneficial medicinal effects including anticancer property. Our novel hypothesis is if Noni juice possesses cancer preventive and/or therapeutic effects. Our preliminary study indicated that the juice made from Tahiti Noni fruits (Tahitian Noni juice, TNJ) is able to reduce DMBA-DNA adducts in rats and mice; to scavenge superoxide free radicals (SAR); to quench lipid peroxides (LPO) in vitro and in vivo; to reduce the inflammatory reaction in a CCI4- induced liver injury model; to selectively inhibit COX-2 in vitro; and to prevent mammary gland tumor at the initiation stage in 'Huggins' tumor model.
The specific aims i n this study are to examine (1) the cancer preventive effect of TNJ at the initiation stage, (2) the therapeutic effect of TNJ at the progression stage, and (3) the preventive mechanisms of TNJ in 'Huggins1 tumorigenic model by pathological and electron microscope examination coupled with a sensitive 32P-postlabeling analysis of DNA adduct formation and enzymatic assays to evaluate the preventive and therapeutic effect of TNJ. The latency, multiplicity, volume of tumors, and the survivor rate of animals at the end of experiment will be evaluated in different groups.