Various
antioxidants in foods, such as phenolic compounds and
carotenoids, were proven to have anticarcinogenic activity. In the case of
carotenoids, the mixture of them was found to be very effective. In fact, the development of
hepatoma in the high risk group of
liver cancer, was significantly suppressed by the treatment with natural
carotenoids mixture. The role of
nitric oxide (NO) in
carcinogenesis has been pointed out, since large quantity of NO has been detected in
cancer tissues, and the expression of inducible
NO synthase (iNOS) was found to correlate with
tumor growth and
metastasis. Recently, we found that NO possessed
tumor initiating activity in mouse skin
carcinogenesis. It has been suggested that some parts of pathological effects induced by NO may depend on
peroxynitrite, an active metabolite of NO. Thus, we accessed the
tumor initiating activity of
peroxynitrite, and found that treatment with
peroxynitrite (initiator) plus TPA (promoter) resulted in the formation of skin
tumors. Under this experimental condition, it has been proven that natural
antioxidants, such as
curcumin and
nobiletin, showed anti-
tumor initiating effect. In the case of
nobiletin, suppressive effect on iNOS induction has also been demonstrated. It is of interest that suppression of iNOS induction was also observed in
phytoene synthase transgenic mouse. After administration of
glycerol (a lung
tumor promoter), lower induction of iNOS gene was observed in lung of the
phytoene producing mice, comparing with that of control mice. Combinational use of various kinds of
antioxidants distributed in foods, e.g., mixture of
carotenoids and
flavonoids, seems to be effective methods for
cancer prevention.