Isoflavone intake inhibits the development of 7,12-dimethylbenz(a)anthracene(DMBA)-induced mammary tumors in normal and ovariectomized rats

Abstract

To determine the associations between isoflavone (49.72% genistin, 5.32% daidzin, 34.54% glycitin) and breast cancer risk, 150 rats were given 5 mg 7,12-dimethylbenz(a)anthracene and half of them were ovariectomized. Then normal rats and ovariectomized rats were divided into 5 groups: control group, isoflavone high (HI), middle (MI), or low (LI) dose group consuming 100, 500, or 1000 mg isoflavones/kg diet, estrogen group (2.5 mg stilboestrol/kg diet). After 24 weeks, tumor incidences were 73% in control group, 7% in HI, 7% in MI, 27% in LI, and 80% in estrogen group for normal rats; 60% in control group, 13% in HI, 7% in MI, 13% in LI, and 73% in estrogen group for ovariectomized rats. Isoflavone treatment decreased tumor incidence and mean tumor number per rat and increased mean latent period compared with those in control group and estrogen group group significantly (p<0.05). The mRNA and protein expression of estrogen receptor β were significantly higher in isoflavone treatment groups than those in control group group. Moreover, isoflavone treatment significantly decreased 8-hydroxydeoxyguanosine content and increased superoxide dismutase level in normal rats and decreased malondialdehyde concentrations in ovariectomized rats compared with control group. In conclusions, isoflavone intake significantly inhibited the development of premenopausal and postmenopausal mammary tumors.

Keywords: estrogen receptor; isoflavones; mammary tumors; ovariectomized rats.

Fig. 1

Body weight curves per week of rats in the 5 groups during the experimental period for normal rats (A) and ovariectomized rats (B). CG; control group, EG; estrogen group, HI; high isoflavone group, MI; middle isoflavone group, LI; low isoflavone group.

Fig. 2

Time course of palpable DMBA-induced mammary tumor appearance during the experimental period: tumor cumulative incidence for normal rats (A) and ovariectomized rats (C); mean tumor number per rat for normal rats (B) and ovariectomized rats (D). CG; control group, EG; estrogen group, HI; high isoflavone group, MI; middle isoflavone group, LI; low isoflavone group.

Fig. 3

The typical image of the tumor and the HE staining of rat mammary tumor. Numerous secondary lumina can be seen in the adenocarcinoma. HE (×250).

Fig. 4

Expression profiles of ERα and ERβ in the mammary tumors in the 5 groups in normal rats. (A and B), ERα. Only LI group presented stronger expression than that in CG group in the mRNA (A) and protein (B) level (*p<0.05). (C and D), ERβ. The mRNA expression (C) and protein expression (D) of ERβ was significantly higher in the isoflavone treatment groups than those in CG group in normal rats (*p<0.05). Error bar, mean and 95% confidence interval of the densitometric values of ERα and ERβ expression in the mammary tumors in the five groups. CG; control group, EG; estrogen group, HI; high isoflavone group, MI; middle isoflavone group, LI; low isoflavone group.

Fig. 5

Expression profiles of ERα and ERβ in the mammary tumors in the 5 groups in ovariectomized rats. (A and B), ERα. ERα expression in HI and MI groups is significantly higher than that in CG group in the mRNA (A) and protein (B) level (*p<0.05). (C and D), ERβ. The mRNA expression (C) and protein expression (D) of ERβ was significantly higher in the isoflavone treatment groups than those in CG group in ovariectomized rats (*p<0.05). Error bar, mean and 95% confidence interval of the densitometric values of ERα and ERβ expression in the mammary tumors in the five groups. CG; control group, EG; estrogen group, HI; high isoflavone group, MI; middle isoflavone group, LI; low isoflavone group.