16. Chemoprevention by Curcumin during Promotion Stage of Tumorigenesis of Mammary Gland in Rats Irradiated with Gamma-rays

Hiroshi Inano and Makoto Onoda

Keywords: chemopreuention, mammary tumor, curcumin

Epidemiological surveys suggest that diet has an impact on cancer incidence. Frequent consumption of vegetables and fruits decreases the risk for human cancer. Recently, attention has been focused on identifying dietary phytochemicals which have an ability to inhibit the processes of carcinogenesis. Extracts of plants or their fractionated ingredtents were found to possess inhibitory effects against chemically induced carcinogenesis. Curcumin (Fig.8) is a major component of turmerie, the dried rhizome of Curcuma longa Linn which is commonly used as a yellow coloring and flavoring agent in food in Asian countries. We have evaluated the chemopreventive effects of curcumin on diethylstilbestrol (DES) induced tumor promotion of rat mammary glands initiated with radiation. Sixty-four pregnant rats received whole body irradiation with 2.6 Gy -rays from a ⁶⁰Co source at day 20 of pregnancy and were divided into 2 groups after weaning. In the control group of 39 rats fed a basal diet and then implanted with a DES pellet for 1 year, 33 (84.6%) developed mammary tumors (Fig.9). Twenty five rats were fed a diet containing 1% curcumin immediately after weaning and received a DES pellet, the same as for the control. The administration of dietary curcumin significantly reduced the incidence (28.O%) of mammary tumors. Also, the incidence (12%) of pituitary tumors in the curcumin-fed rats was about one-fifth of that (56%) in the control rats. Multiplicity and Iballs index of mammary tumors were decreased by curcumin. Rats fed the curcumin diet showed a reduced incidence of the development of both mammary adenocarcinoma and ER(+)PgR(+) tumor in comparison with the control group. By long-term treatment of curcumin, body weight and ovarian weight were reduced, but liver weight was increased. Compared with the control rats, the curcumin-fed rats showed a significant reduction of serum prolactin, whereas, estradiol-17 and progesterone concentrations were not significantly different between the two groups. Curcumin did not have any effeet on the concentration of free cholesterol, cholesterol ester and triglyceride. Feeding of the curcumin dietcaused a significant increase of the concentrations of tetrahydrocurcumin, arachidonic acid and eicosapentaenoic acid, and a significant decrease of TBARS concentration in serum. Whole mounts of the mammary glands showed that curcumin yielded morphologically indistinguishable proliferation and differentiation from the glands of the control rats. These findings suggest that curcumin has a potent preventive activity during the DES-dependent promotion stage of radiation-induced mammary tumorugenesis.

Fig.8. Chemical structure of curcumin. Chemical name: 1,7-bis (4'-hydroxy-3'-methoxyphenyl)-1,6-heptadiene-3,5-dione.	Fig.9. Incidence for mammary tumors and pituitary tumors in -ray-irradiated rats. Columns and vertical bars represent incidence(%) of tumor and standard deviation, respectivery. The numbers in parentheses on the top of the bar represent the actual number of rats bearing tumors per rats used.

Publication:
Inano, H., Onoda, M., Inafuku, N., Kubota, M. Kamada, Y., Osawa, T., Kobayashi, H. and Wakabayashi, K.: Carcinogenesis, 20, 1011-1018, 1999.