The results of the present study show that tea components significantly lowered body weights without significantly altering food intakes. Whole teas, but not tea polyphenol extracts, significantly lowered WAT mass by 65–70% in male mice and by 43–60% in female mice. SPC and teas, alone and in combination, significantly lowered serum leptin concentrations in both male and female mice. The combination of SPC and GT lowered serum IGF-I concentrations in both male and female mice in a synergistic manner. The SPC and tea combinations also lowered serum estrogen concentrations in female mice in a synergistic manner. Our results suggest that the combinations of soy and tea components may improve metabolic conditions by inhibiting abdominal WAT mass and by modulating certain MS-associated elements such as leptin, IGF-I, and sex hormones.
In this animal study, MS was not induced and the animals were treated with a 10%-fat diet. Even in this situation, the soy and tea components, especially in combinations, showed significant modulation of several MS-related elements, such as leptin, IGF-I, and sex hormones, all favoring cancer-prevention activity. Indeed, the SPC and tea combinations inhibited the growth and progression of both breast and prostate tumors in our preclinical animal models. These findings may have significant effects on the prevention of breast cancer or prostate cancer in a healthy population because the dietary fat was at a “normal” level. Although not conducted in this report, we expect that certain soy and tea combinations may significantly prevent the development of MS and improve metabolic status. To directly establish the cancer-promoting effects of MS, it is also required to determine whether MS enhances the development or progression of breast or prostate cancer in appropriate animal models. Further animal studies are also required to define whether certain soy and tea combinations effectively prevent breast or prostate cancer in part by preventing the development of MS and improving metabolic profiles.
Previous research has primarily focused on the cancer prevention activity of soy or tea components alone (18
) but not in combination. Evidence is emerging that soy components, such as soy isoflavones and soy protein, may play a beneficial role in obesity and diabetes. Soy protein associated with isoflavones improves glucose control, lipid profiles, and insulin resistance (24
) and increases the serum adiponectin concentration (27
). Soy isoflavones significantly lower fat mass, plasma glucose in both lean and obese rats (30
), and serum concentrations of leptin (32
) and improve glucose tolerance (34
). Clinical intervention studies showed that soyfood reduces serum concentrations of insulin and leptin (35
). Consumption of soy isoflavones is associated with lower body mass indexes and fasting insulin concentrations and higher HDL cholesterol and also lowers the insulin response to an oral glucose load in presumably normal-weight, postmenopausal women (36
). Thus, it appears from these studies that soy-based diets may provide potential benefits in conditions associated with impaired glucose tolerance, hyperlipidemia, and reduced insulin sensitivity. On the other hand, some studies did not show significant effects of soy components on metabolic profiles (37
Similar to the soy studies, previous studies have shown the MS-preventive activity of tea components. Tea components, especially epigallocatechin gallate, had antiobesity activity and improved metabolic disorders via modulation of adipokines and growth factors (39
), especially suppression of leptin concentrations (39
). Besides tea polyphenols, caffeine had antiobesity activity and modulated related adipokines such as leptin (43
). GT lowered adipose tissue weight without any change in body weight, other tissue weights, and food and water intakes, and also significantly lowered the plasma concentrations of cholesterol and free fatty acids (41
Our results suggest that one of the mechanisms by which SPC and tea combinations may have synergistic cancer prevention activity is via synergistic effects on lowering IGF-I concentrations. IGF-I has been shown to play an important role in the development of breast and prostate glands and in carcinogenesis and tumorigenesis. Epidemiologic investigations in general indicated that the increased serum concentrations of IGF-I were significantly associated with breast cancer risk (44
) and prostate cancer risk (46
). On the other hand, the results from epidemiologic investigations on the association between soy components, mostly soy proteins, and serum concentrations of IGF-I are inconsistent, ranging from a positive association (48
), a negative association (55
), to no association (55
). Our results showed that although SPC and tea alone did not have significant effects on serum IGF-I concentrations, the combination of SPC and GT significantly lowered IGF-I concentrations in a synergistic manner. Our results support further investigation to apply appropriate dietary combination regimens, such as soy and tea combinations, for cancer prevention by targeting IGF-I function.
Our results also showed that SPC and tea combinations had a synergistic effect on lowering the serum estrogen concentration in female mice. Estrogen plays a key role in estrogen-dependent breast cancer development and growth. Obesity has been shown to enhance circulating concentrations of estrogen and thus may favor promotion of breast cancer development. Administration of anti-estrogen tamoxifen is a successful adjuvant therapy for patients with estrogen-dependent breast cancer and significantly improves the survival of those women (60
). The results from our study may provide a mechanistic explanation for the finding in our breast cancer study of a synergistic effect of SPC and GT on inhibiting the growth of breast tumors (21
). Further research is warranted to investigate the mechanisms by which SPC and tea combinations may reduce circulating estrogen concentrations in a synergistic manner.
Our results also showed that the combination of BT or GT with SPC reduced leptin concentrations in a synergistic manner in female mice. Due to dramatic effects of soy and tea treatment alone, the potentiating effects between soy and tea combinations were not apparent in male mice. Plasma leptin concentrations correlate with fat stores and the volume and number of adipocytes. Epidemiologic and experimental studies in general have shown that leptin promotes the development and progression of breast cancer (61
) and prostate cancer (66
). Our findings suggest that one of the mechanisms by which the soy and tea combination may synergistically prevent breast cancer may be through synergistic effects on lowering leptin concentrations in female mice.
In summary, the results of the present study show that the soy and tea combinations lowered abdominal WAT mass, serum concentrations of IGF-I and leptin in both male and female mice, and estrogen concentrations in female mice in a synergistic or an additive manner. The results suggest that the soy and tea combination may prevent MS and improve metabolic profiles, and this MS-preventive activity may be in part responsible for the synergistic effects of the soy and tea combinations on the prevention of breast or prostate cancer observed in the animal studies. The results provide the rationale to support future research to define the causal role of MS in the development and progression of breast or prostate cancer and to apply dietary combination strategies, such as the soy and tea combinations, to cancer prevention by preventing MS.