The present study was designed to investigate differences in how dietary blueberries and black raspberries may prevent breast cancer. The authors previously demonstrated that berries in the diet of ACI rats provided protection against estrogen-induced mammary tumorigenesis. In the current study, rats were administered a diet containing 5% blueberry or black raspberry two weeks before implantation with 9 mg 17β-estradiol. Rats were killed at three weeks, three months and approximately seven months (when tumor incidence in the control group that did not receive berries reached 80%). The berry diets were associated with significantly reduced (p<0.05) tumor volume (control: 801.2±105.3 mm3; blueberry: 395±97.9 mm3; black raspberry: 461±109.8 mm3) and tumor multiplicity (control: 6.9±0.9; blueberry: 4.4±0.6; black raspberry: 4.3±0.6). Importantly, while blueberry resulted in lower tumor volume than black raspberry, black raspberry was more effective in delaying the first tumor incidence, by five weeks (p<0.05). In further studies, key molecules of cell-cycle regulation, cell proliferation and transcription were investigated. Estrogen treatment up-regulated the cell-cycle regulatory molecule cyclin D1 by 3-4-fold in mammary tissues. However, cyclin D1 was significantly down-regulated by the blueberry diet as early as three weeks after estradiol implantation and remained down-regulated during the entire tumorigenesis period, as shown by Western blot analysis. On the other hand, the black raspberry diet did not result in any significant down-regulation of cyclin D1. Estrogen receptor α, which was significantly overexpressed at all three time points after estradiol administration, was significantly offset by the black raspberry diet whereas this effect was less pronounced in mice on the blueberry diet. While blueberry contains five different anthocyanidins (delphinidin, cyanidin, malvidin, peonidin, and petunidin) and insignificant levels of ellagic acid, black raspberry contains primarily the anthocyanidin cyanidin and high levels of ellagic acid. The authors conclude that the distinct and specific molecular targets and pathways involved in the protective actions of the two berries are derived from their distinct phytochemical signatures.

The present study was designed to determine the antioxidant capacity, vitamin C content, and polyphenolic compounds of black currant, blueberry, raspberry, red currant, and cranberry extracts. The antioxidant capacity was determined using the FRAP (ferric reducing ability of plasma) assay, a simple test of total antioxidant power. The vitamin C and phenolic and polyphenolic compounds contents of the berries was determined by reversed-phase HPLC-PDA-MS3 and reversed-phase HPLC-PDA with an online antioxidant detection system. A variety of anthocyanins were found to be the major contributor to the antioxidant capacity of black currants and blueberries. Lower antioxidant capacity was found for red currants and cranberries; this appeared to be due mainly to the lower anthocyanin content of these berries. Raspberries also were found to have a lower anthocyanin content than black currants and blueberries. However, this did not translate into significantly lower antioxidant capacity because raspberries contain the ellagitannins sanguin H-6 and lambertianin C. These ellagitannins were responsible for 58% of the antioxidant capacity of the raspberries. Vitamin C was responsible for 18% to 23% of the antioxidant capacity of black currants, red currants, and cranberries, as well as 11% of the antioxidant capacity of raspberries. However, the vitamin C content of the blueberry extract was not significant and did not contribute to its antioxidant capacity. The cranberry extract contained procyanidin dimers, which contributed 7% of its antioxidant capacity. However, the authors were unable to measure the contribution of polymeric proanthocyanidins to the antioxidant capacity of the five berries since they were not amenable to analysis by reversed-phase HPLC.

The apparent anti-cancer properties of black raspberries and blueberries may be in part due to the inhibition of mammary cell proliferation. Female rats prone to breast cancer were divided into four groups, each receiving either a control diet or a diet supplemented with powder of black raspberry or blueberry. Two weeks later three groups, one on the control diet and the other two on berry diets, were treated with subcutaneous estradiol implants. Three weeks after this treatment, all three groups showed increased mammary cell proliferation. However, the blueberry diet resulted in a proliferation index 66% lower than the control diet, and the index was also 32% lower in the mice fed the black raspberry diet. The authors examined whether the antiproliferative activity of the berries correlated with their bioactive contents by analyzing the total phenolic and anthocyanin contents. They found that, contrary to expectations, the black raspberry powder had a higher total phenolic content than the blueberry powder and the difference in the anthocyanin content was even greater. This suggests that other attributes or the particular combination of phytochemicals in blueberries might provide additive or synergistic benefits.

The current study investigated the ability of dietary berries and ellagic acid to reduce estrogen-mediated mammary tumorigenesis. It has been demonstrated that estrogen acts as a complete mammary carcinogen in ACI rats. This animal model enabled the researchers to perform prevention studies to identify compounds that are effective against estrogen-induced breast cancer. Eight to nine week old female ACI rats were fed either an AIN-93M diet (n = 25), or a diet supplemented with powdered blueberry (n = 19) at 2.5% wt/wt, powdered black raspberry (n = 19) at 2.5% wt/wt, or ellagic acid (n = 22) at 400 ppm. The animals received implants of 17beta-estradiol two weeks later, were palpated periodically for mammary tumors, and were euthanized after 24 weeks. No differences were found in tumor incidence at 24 weeks. However, tumor volume and multiplicity were reduced significantly after dietary intervention. Compared with the control group, ellagic acid was found to reduce mammary tumor volume by 75% (P < 0.005) and tumor multiplicity by 44% (P < 0.05). Black raspberry was almost as effective, with tumor volume diminished by > 69% (P < 0.005) and tumor multiplicity by 37% (P = 0.07). Blueberry showed a 40% reduction in tumor volume, with no significant reduction in tumor multiplicity. The authors conclude that both ellagic acid and berries are effective in the prevention of solely estrogen-induced mammary tumors.

In the present study, extracts of six berries (blackberry, black raspberry, blueberry, cranberry, red raspberry and strawberry) were evaluated for their phenolic constituents and ability to inhibit growth of various human cancer cell lines. Berries contain a remarkable range of phytochemicals with biological properties such as anti-inflammatory, antioxidant, anticancer, and anti-neurodegenerative activities. The main classes of berry phenolics were found to be anthocyanins, proanthocyanidins, flavonols, ellagitannins, gallotannins, and phenolic acids. The berry extracts were evaluated for their ability to inhibit the growth of human oral (KB, CAL-27), breast (MCF-7), prostate (LNCaP), and colon (HT-29, HCT116) cancer cell lines at concentrations varying from 25 to 200 μg/mL. The growth of all the tumor cells was found to be inhibited increasingly with increasing concentrations of berry extract, with different degrees of potency for different berries and cell lines. The extracts were also evaluated for their ability to increase apoptosis of the COX-2 expressing colon cancer cell line, HT-29. Black raspberry and strawberry extracts were found to have the most significant pro-apoptotic effects against these cells.

Rats with the esophageal cancer were treated with N-nitrosomethylbenzylamine (NMBA) three times per week for five weeks. Beginning one week later, the rats were fed a diet containing 5% black raspberries for the remainder of the study. At week 25, black raspberries were found to inhibit tumor multiplicity. Black raspberries reduced mRNA and protein expression levels of COX-2, iNOS, and c-Jun as well as the level of prostaglandin E2 in preneoplastic lesions of the esophagus. The authors conclude that black raspberries may have a novel tumor suppressive role through inhibition of COX-2, iNOS, and c-Jun.

The present study investigated the effects of extracts of blueberries, black currant, black chokeberries, apple, sea buckthorn, plum, lingonberries, cherries, and raspberries on proliferation of hormone receptor positive breast cancer cells. The extracts decreased the proliferation of breast cancer cells and the effect was proportional to concentration. There were great variations in the antioxidants, cartenoids, flavonols, hydroxycinnamic acids, anthocyanins, phenolics and Vitamin C in the extracts. The antiproliferative effects correlated with levels of some carotenoids and with vitamin C levels. The same inhibition of cell proliferation could not be found using Vitamin C alone, suggesting a possible synergistic effect of Vitamin C and other substances.

Fresh juice and extracts of strawberry, blueberry, and raspberry fruits were tested for their ability to inhibit the formation of mutations by methyl methanesulfonate and benzo a pyrene, known carcinogens. All three juices significantly inhibited mutagenesis by both carcinogens. Of the extracts, the hydrolyzable tannin-containing fraction of ethanol strawberry extract was the most effective at inhibiting mutations.

The female hormone, 17ß-estradiol (E2) is a known risk factor in the development of breast cancer. In this study, female ACI rats were implanted with E2-filled silastic tubes. The rats were provided either a control diet or a diet supplemented with 2.5% powdered mixed berries (1:1 mixture of strawberries, raspberries, blueberries, blackberries and black raspberries), 2.5% blueberries, 2.5% blueberries plus ellagic acid, or ellagic acid. Compared to the control diet, the adduct (cancer-causing enzymes) levels were significantly decreased by the test diets: The P-1 adducts were reduced by >75% with blueberries and >50% each with blueberries plus ellagic acid, and ellagic acid alone. Ellagic acid was more effective (60%) in diminishing the P-2 adducts, followed by blueberries, or blueberries plus ellagic acid (30-40 %). The mixed berries, however showed no change in the adduct levels.

Four fresh raspberry varieties (Heritage, Kiwigold, Goldie, and Anne) were evaluated for antioxidant and antiproliferative properties. The total phenolic content, total flavonoids and total antioxidant activity of the raspberries were measured and ranked as follows: Heritage, Kiwigold, Goldie, and Anne. The color of the raspberry juice of each variety correlated with its total phenolic, flavonoid, and anthocyanin contents. The proliferation of human liver cancer cells was found to be significantly inhibited in a dose-dependent manner by exposure to the raspberry extracts. However, no relationship was found between antiproliferative activity and the total amount of phenolics/flavonoids found in the each raspberry variety.

Blueberry and strawberry extracts were tested against cultures of two aggressive cervical cancer cell lines and two breast cancer cell lines. The extracts significantly decreased the growth of both cervical and hormone receptor positive breast cancer cells. Strawberry extract was more effective in decreasing the growth of breast cancer cells whereas blueberry extract demonstrated more growth inhibition of cervical cancer cells. In addition, an aqueous extract of raspberry and an ethanol extract of blueberry both were found to inhibit mutagenesis by carcinogens.