Chemoprevention of N‐Nitroso‐N‐methylurea‐induced Rat Mammary Cancer by Miso and Tamoxifen, Alone and in Combination

Abstract

We examined the effects of a Japanese fermented soybean product, miso, and tamoxifen (TAM), alone and in combination, on N-nitroso-N-methylurea (MNU)-induced rat mammary cancer. Seven-week-old female CD/Crj rats received a single i.v. dose (50 mg/kg body weight) of MNU. After administration of MNU, the rats were divided into 4 groups: regular diet (control), 10% miso diet, regular diet+ + + +TAM, and 10% miso diet+ + + +TAM. TAM was implanted s.c. in the form of pellets containing 2.5 mg at the same time as MNU was administered. All rats were observed for 18 weeks after MNU administration. Incidence (percentage of rats with tumors) and multiplicity (mean tumors/rat) of mammary tumors were 91% and 4.5 in the control, 77% and 2.4 (P< < < <0.05) in the 10% miso group, 68% and 1.4 (P< < < <0.01) in the TAM group, and 10% (P< < < <0.0001 or less) and 0.2 (P< < < <0.0001) in the 10% miso+ + + +TAM group. In the second experiment, the effect of the combination of miso and TAM on established rat mammary tumors was investigated. When the mammary tumors induced by MNU reached 10 to 25 mm, the rats were divided into 3 treatment groups: regular diet, regular diet+ + + +TAM, and 10% miso diet+ + + +TAM. At 6 weeks after the start of treatment, the mean tumor size in the control and TAM groups was 160% and 141% of the pretreatment value, but a decrease to 85% of the pretreatment value was produced by the combination of miso and TAM, and this was significantly different from both the control and TAM groups (P< < < <0.01 and P< < < <0.05, respectively). These results indicate that miso is useful in protecting against mammary cancer and it can be expected to have a potent antitumor effect, especially when used in combination with TAM.

Soy isoflavones and risk of cancer recurrence in a cohort of breast cancer survivors: the Life After Cancer Epidemiology study

“…A cross-sectional study among Asian-American women with breast cancer found no evidence that soy intake adversely affected levels of circulating tamoxifen [41], implying that isoflavones presumably do not interfere with tamoxifen binding to estrogen receptors. Furthermore, soy protein isolates or soy-based miso in combination with tamoxifen were found to be more effective than tamoxifen alone in preventing chemically-induced rat mammary cancers [42, 43]. Isoflavones may also prevent the formation of carcinogenic metabolites of tamoxifen via inhibition of the cytochrome P450 enzymes, thereby making this synergistic interaction a more effective therapy for breast cancer survivors [44].…”

Effects of phyto-oestrogens on tissues

“…As pointed out earlier, however, tumour inhibition appeared to be related to a delay in tumour appearance in the rats consuming whole soyabeans. In a follow-up study (Gotoh et al 1998a), a diet containing 100 g misoakg diet was again shown to be effective in reducing tumour number by about 50 %. In addition, tamoxifen also signi®cantly reduced tumour number, and the combination of tamoxifen and miso acted synergistically to inhibit tumour development.…”

Neoplasia in Zebrafish (Danio rerio) Treated with N-methyl-N'nitro-N-nitrosoguanidine by Three Exposure Routes at ifferent Developmental Stages

“…Fibrosarcoma occurs in rats injected subcutaneously with MNNG (37). Other members of the broad family of Nnitroso compounds target many tissue sites, causing neoplasia of oral, esophageal, nasal, lung, kidney, urinary bladder, mammary, thyroid, and pancreatic tissue in mammals (6,11,12). Transplacental or perinatal exposure of mammals to N-nitroso agents including nitrosoureas may induce a high incidence of neural, ocular, and to a lesser extent odontogenic neoplasia (25,32,39).…”