A combination of green tea extract, specific nutrient mixture and quercetin: An effective intervention treatment for the regression of N-methyl-N-nitrosourea (MNU)-induced mammary tumors in Wistar rats

Abstract

Abstract. Mammary tumors were developed by intraperitoneal injection of N-methyl-N-nitrosourea (MNU) in 21-day-old, sexually immature female Wistar rats. Injection of MNU was repeated 14 weeks after the first one. When palpable tumors were evident in all of the rats, various dietary treatments were initiated for a period of 8 weeks. The treatments were designed to provide 30 mg green tea extract either alone or as a nutrient mixture (E). E was then expanded to include either a nutrient supplement (N), quercetin (Q) or both (N+Q). At the end of the treatment, tumor size/rat measured in the live rats was significantly lower in the groups receiving E, E+Q, E+N and E+N+Q than in the positive control (PC) group which did not receive any dietary treatment. Tumor number/ rat, tumor volume/rat and tumor weight/rat were evaluated after sacrificing the rats on the 60th day. The rats receiving E+N+Q showed significantly lower values for the three parameters as compared to the PC group. The PC group showed 24 carcinomas mostly of grade III severity, while the E+N+Q group had only 6 carcinomas, all of which were of grade II severity. IntroductionN-methyl-N-nitrosourea (MNU)-induced mammary carcinogenesis in female rats is frequently used as an animal model for the investigation of breast carcinogenesis and the treatment of breast cancer in humans (1-12). In our previous studies with MNU-induced rat mammary carcinogenesis, we observed that the specific formulation of nutrient supplements containing ascorbic acid, L-lysine, L-proline, L-arginine, N-acetyl cysteine selenium, copper and manganese along with green tea extract (GTE) fed to the animals reduced the incidence, number and weights of the tumors (12) measured 30 weeks post-MNU. The combination was designated by the authors as 'Nutrient Synergy' (NS) to underscore the synergistic action of various constituents. The beneficial results obtained in the studies were mainly attributed to epigallocatechin-3-gallate (EGCG), the principal anticancer agent present in the GTE in the NS (13,14). Our previous in vitro studies with cancer cell lines demonstrated that an increase in the concentration of EGCG in the cell culture media resulted in increased anticancer activity. These findings suggested that when the plasma levels of EGCG are increased, this increase is reflected in the elevated anticancer activity. Our recent investigation (15) showed that the plasma level of EGCG in rats was elevated by as much as 25% when a small amount of quercetin (Q) was administered along with GTE as a nutrient mixture (E) + nutrient supplement (N). It was therefore hypothesized that the anticancer activity of E is enhanced when Q is fed in combination with E+N.Our previous MNU study (12), based on previous investigations, was conducted for as extensive a period as 30 weeks following the MNU injection. Various studies by Thompson and associates (6,8,16) indicated that the prolonged period of experimentation of such studies can be considerably reduced when MNU is administered to 21-day-old sexually...

Anticancer Efficacy of Polyphenols and Their Combinations

“…We observed that including quercetin in the nutrient mixture containing EGCG has beneficial effects when administered to rats at early stages of breast tumor growth. Breast tumors were induced by IP administration of N -methyl- N -nitrosourea to Wistar rats [ 108 ]. After tumors were evident in all rats, the animals were divided into groups and fed one of the following regimens for 60 days: control diet; 30 mg green tea extract alone; 30 mg green tea extract in combination with NM; or a diet containing 30 mg of green tea extract, NM and quercetin.…”

“…The results showed that tumor size/rat was significantly lower in all supplemented groups than in the Control group. The rats on the diet containing NM and quercetin showed significantly lower values for tumor incidence, mean tumor volume and mean tumor weight compared to the Control, the green tea extract and the NM groups [ 108 ]. Rats in the Control group developed 24 carcinomas (mostly of grade III severity), contrasted with six carcinomas (all of which were of grade II severity) in the NM supplemented group containing quercetin.…”

Micronutrient synergy—a new tool in effective control of metastasis and other key mechanisms of cancer

“…The synergistic anticancer effect of micronutrients is exemplified in the study of Kale et al [ 33 ] on the treatment of N-methyl-N-nitrosourea (MNU)-induced mammary tumors in Wistar rats. Different micronutrient treatment regimens were provided after rats had developed palpable tumors to correspond to intervention treatment approaches in clinical settings.…”

Methodological problems with population cancer studies: The forgotten confounding factors

“…When the Rath-Pauling compound was tested alone in rats having a chemically induced mammary carcinoma, researchers demonstrated greater cancer inhibition than when green tea extract was used alone. [ 31 ] Adding quercetin and other micronutrients further enhanced the cancer-inhibiting effects of the base mixture. Not only were the tumors smaller, but also the number of metastatic nodules was reduced from 24 in the control animals to 6 nodules in the treated animals.…”