Cancer prevention by antioxidants.
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.
Nishino
Hoyoku
H
Department of Biochemistry and Molecular Biology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan. hnishino@basic.kpu-m.ac.jp
Tokuda
Harukuni
H
Satomi
Yoshiko
Y
Masuda
Mitsuharu
M
Osaka
Yasuhito
Y
Yogosawa
Shingo
S
Wada
Saeri
S
Mou
Xiao Yang
XY
Takayasu
Junko
J
Murakoshi
Michiaki
M
Jinnno
Kenji
K
Yano
Masamichi
M
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D001628:Beverages; D002338:Carotenoids / Q000494:pharmacology; D003474:Curcumin / Q000627:therapeutic use; D000077276:Lycopene; D018551:Solanum lycopersicum; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008815:Mice, Inbred Strains; D030421:Peroxynitrous Acid; D012878:Skin Neoplasms / Q000139:chemically induced / Q000517:prevention & control; D013755:Tetradecanoylphorbol Acetate
D016588:Anticarcinogenic Agents; D000975:Antioxidants; D030421:Peroxynitrous Acid; D002338:Carotenoids; D003474:Curcumin; D013755:Tetradecanoylphorbol Acetate; D000077276:Lycopene