Blueberry and Cancer

In a 2005 study extracts were made of blueberry phenols, which were freeze dried and further separated into phenolic acids, tannins, flavanols and anthocyanins. The dried extracts were then added to cell cultures containing two colon cancer cell lines – HT 29 and Caco-2. In concentrations normally found in rat plasma after eating blueberries, anthocyanin fractions increased DNA fragmentation – a indication that apostosis had been triggered – by between 2 and 7 times. Flavanol and tannin extracts cut cell proliferation time in half at concentrations of 70-100 and 50-100 microg/mL. The phenolic fraction reduced proliferation by a half at a concentration of 1000 microg/mL (Yi W, Fischer J, Krewer G, Akoh CC. Phenolic compounds from blueberries can inhibit colon cancer cell proliferation and induce apoptosis. J Agric Food Chem. 2005 Sep 7;53(18):7320-9).

Blueberries contain another antioxidant compound called ellagic acid, which blocks metabolic pathways that can lead to cancer. A study involving 1,271 subjects, showed that those who ate the most strawberries (another food high in ellagic acid) were three times less likely to develop cancer than those who ate few or no strawberries (Hannum SM. Potential impact of strawberries on human health: a review of the science. Crit Rev Food Sci Nutr. 44, 1:1-17, 2004).

Clinical Abstracts

Phenolic compounds from blueberries can inhibit colon cancer cell proliferation and induce apoptosis.

J Agric Food Chem. 2005 Sep 7;53(18):7320-9

Yi W, Fischer J, Krewer G, Akoh CC.

Department of Food Science and Technology, The University of Georgia, Athens, Georgia 30602-7610, USA.

Research has shown that diets rich in phenolic compounds may be associated with lower risks of several chronic diseases including cancer. This study systematically evaluated the bioactivities of phenolic compounds in rabbiteye blueberries and assessed their potential antiproliferation and apoptosis induction effects using two colon cancer cell lines, HT-29 and Caco-2. Polyphenols in three blueberry cultivars, Briteblue, Tifblue, and Powderblue, were extracted and freeze-dried. The extracts were further separated into phenolic acids, tannins, flavonols, and anthocyanins using an HLB cartridge and LH20 column. Some individual phenolic acids and flavonoids were identified by HPLC with >90% purity in anthocyanin fractions. The dried extracts and fractions were added to the cell culture medium to test for antiproliferation activities and induction of apoptosis. Flavonol and tannin fractions resulted in 50% inhibition of cell proliferation at concentrations of 70-100 and 50-100 microg/mL in HT-29 and Caco-2 cells, respectively. The phenolic acid fraction showed relatively lower bioactivities with 50% inhibition at approximately 1000 microg/mL. The greatest antiproliferation effect among all four fractions was from the anthocyanin fractions. Both HT-29 and Caco-2 cell growth was significantly inhibited by >50% by the anthocyanin fractions at concentrations of 15-50 microg/mL. Anthocyanin fractions also resulted in 2-7 times increases in DNA fragmentation, indicating the induction of apoptosis. The effective dosage levels are close to the reported range of anthocyanin concentrations in rat plasma. These findings suggest that blueberry intake may reduce colon cancer risk.

PMID: 16131149 [PubMed - indexed for MEDLINE]

Blackberry, black raspberry, blueberry, cranberry, red raspberry, and strawberry extracts inhibit growth and stimulate apoptosis of human cancer cells in vitro.

J Agric Food Chem. 2006 Dec 13;54(25):9329-39

Seeram NP, Adams LS, Zhang Y, Lee R, Sand D, Scheuller HS, Heber D.

Center for Human Nutrition, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA. nseeram@mednet.ucla.edu

Berry fruits are widely consumed in our diet and have attracted much attention due to their potential human health benefits. Berries contain a diverse range of phytochemicals with biological properties such as antioxidant, anticancer, anti-neurodegerative, and anti-inflammatory activities. In the current study, extracts of six popularly consumed berries--blackberry, black raspberry, blueberry, cranberry, red raspberry and strawberry--were evaluated for their phenolic constituents using high performance liquid chromatography with ultraviolet (HPLC-UV) and electrospray ionization mass spectrometry (LC-ESI-MS) detection. The major classes of berry phenolics were anthocyanins, flavonols, flavanols, ellagitannins, gallotannins, proanthocyanidins, and phenolic acids. The berry extracts were evaluated for their ability to inhibit the growth of human oral (KB, CAL-27), breast (MCF-7), colon (HT-29, HCT116), and prostate (LNCaP) tumor cell lines at concentrations ranging from 25 to 200 micro g/mL. With increasing concentration of berry extract, increasing inhibition of cell proliferation in all of the cell lines were observed, with different degrees of potency between cell lines. The berry extracts were also evaluated for their ability to stimulate apoptosis of the COX-2 expressing colon cancer cell line, HT-29. Black raspberry and strawberry extracts showed the most significant pro-apoptotic effects against this cell line. The data provided by the current study and from other laboratories warrants further investigation into the chemopreventive and chemotherapeutic effects of berries using in vivo models.

PMID: 17147415 [PubMed - in process]

Absorption of anthocyanins from blueberry extracts by caco-2 human intestinal cell monolayers.

J Agric Food Chem. 2006 Jul 26;54(15):5651-8.

Yi W, Akoh CC, Fischer J, Krewer G.

Department of Food Science and Technology, The University of Georgia, Athens, Georgia 30602, USA.

Recent studies have shown that dietary polyphenols may contribute to the prevention of cardiovascular disease and cancer. Anthocyanins from different plant sources including blueberries have been shown to possess potential anticancer activities. One of the key factors needed to correctly relate the in vitro study results to human disease outcomes is information about bioavailability. The objectives of the current study were to evaluate the absorption of blueberry anthocyanin extracts using Caco-2 human intestinal cell monolayers and investigate the effects of different aglycones, sugar moieties, and chemical structure on bioavailability of different types of anthocyanins. The results of this study showed that anthocyanins from blueberries could be transported through the Caco-2 cell monolayers although the transport/absorption efficiency was relatively low compared to other aglycone polyphenols. The transport efficiency of anthocyanins averaged approximately 3-4% [less than 1% in delphinidin glucoside (Dp-glc)]. No significant difference in transport/absorption efficiency was observed among three blueberry cultivars. The observed trends among different anthocyanins generally agreed well with some published in vivo results. Dp-glc showed the lowest transport/absorption efficiency, and malvidin glucoside (Mv-glc) showed the highest transport/absorption efficiency. Our result indicates that more free hydroxyl groups and less OCH(3) groups can decrease the bioavailability of anthocyanins. In addition, cyanindin glucoside (Cy-glc) showed significantly higher transport efficiency than cyanidin galactoside (Cy-gal), and peonidin glucoside (Pn-glc) showed significantly higher transport efficiency than peonidin galactoside (Pn-gal), indicating that glucose-based anthocyanins have higher bioavailability than galactose-based anthocyanins.

PMID: 16848559 [PubMed - indexed for MEDLINE]

Differential effects of blueberry proanthocyanidins on androgen sensitive and insensitive human prostate cancer cell lines.

Cancer Lett. 2006 Jan 18;231(2):240-6

Schmidt BM, Erdman JW Jr, Lila MA.

Department of Natural Resources and Environmental Sciences, University of Illinois at Urbana-Champaign, 1201 S. Dorner Dr, Urbana, IL 61801, USA.

Blueberries are rich in health-promoting polyphenolic compounds including proanthocyanidins. The purpose of this study was to determine if proanthocyanidin-rich fractions from both wild and cultivated blueberry fruit have the same inhibitory effects on the proliferation of LNCaP, an androgen-sensitive prostate cancer cell line, and DU145, a more aggressive androgen insensitive prostate cancer cell line. When 20 microg/ml of a wild blueberry proanthocyanidin fraction (fraction 5) was added to LNCaP media, growth was inhibited to 11% of control with an IC50 of 13.3 microg/ml. Two similar proanthocyanidin-rich fractions from cultivated blueberries (fractions 4 and 5) at the same concentration inhibited LNCaP growth to 57 and 26% of control with an IC50 of 22.7 and 5.8 microg/ml, respectively. In DU145 cells, the only fraction that significantly reduced growth compared to control was fraction 4 from cultivated blueberries with an IC50 value of 74.4 microg/ml, indicating only minor inhibitory activity. Differences in cell growth inhibition of LNCaP and DU145 cell lines by blueberry fractions rich in proanthocyanidins indicate that blueberry proanthocyanidins have an effect primarily on androgen-dependant growth of prostate cancer cells. Possible molecular mechanisms for growth inhibition are reviewed.

PMID: 16399225 [PubMed - indexed for MEDLINE]

Blueberry flavonoids inhibit matrix metalloproteinase activity in DU145 human prostate cancer cells.

Biochem Cell Biol. 2005 Oct;83(5):637-43.

Matchett MD, MacKinnon SL, Sweeney MI, Gottschall-Pass KT, Hurta RA.

Department of Biology, University of Prince Edward Island, 550 UniversityAve., Charlottetown, PE C1A 4P3, Canada.

Regulation of the matrix metalloproteinases (MMPs), the major mediators of extracellular matrix (ECM) degradation, is crucial to regulate ECM proteolysis, which is important in metastasis. This study examined the effects of 3 flavonoid-enriched fractions (a crude fraction, an anthocyanin-enriched fraction, and a proanthocyanidin-enriched fraction), which were prepared from lowbush blueberries (Vaccinium angustifolium), on MMP activity in DU145 human prostate cancer cells in vitro. Using gelatin gel electrophoresis, MMP activity was evaluated from cells after 24-hr exposure to blueberry fractions. All fractions elicited an ability to decrease the activity of MMP-2 and MMP-9. Of the fractions tested, the proanthocyanidin-enriched fraction was found to be the most effective at inhibiting MMP activity in these cells. No induction of either necrotic or apoptotic cell death was noted in these cells in response to treatment with the blueberry fractions. These findings indicate that flavonoids from blueberry possess the ability to effectively decrease MMP activity, which may decrease overall ECM degradation. This ability may be important in controlling tumor metastasis formation.

PMID: 16234852 [PubMed - indexed for MEDLINE]

Phenolic compounds from blueberries can inhibit colon cancer cell proliferation and induce apoptosis.

J Agric Food Chem. 2005 Sep 7;53(18):7320-9

Yi W, Fischer J, Krewer G, Akoh CC.

Department of Food Science and Technology, The University of Georgia, Athens, Georgia 30602-7610, USA.

Research has shown that diets rich in phenolic compounds may be associated with lower risks of several chronic diseases including cancer. This study systematically evaluated the bioactivities of phenolic compounds in rabbiteye blueberries and assessed their potential antiproliferation and apoptosis induction effects using two colon cancer cell lines, HT-29 and Caco-2. Polyphenols in three blueberry cultivars, Briteblue, Tifblue, and Powderblue, were extracted and freeze-dried. The extracts were further separated into phenolic acids, tannins, flavonols, and anthocyanins using an HLB cartridge and LH20 column. Some individual phenolic acids and flavonoids were identified by HPLC with >90% purity in anthocyanin fractions. The dried extracts and fractions were added to the cell culture medium to test for antiproliferation activities and induction of apoptosis. Flavonol and tannin fractions resulted in 50% inhibition of cell proliferation at concentrations of 70-100 and 50-100 microg/mL in HT-29 and Caco-2 cells, respectively. The phenolic acid fraction showed relatively lower bioactivities with 50% inhibition at approximately 1000 microg/mL. The greatest antiproliferation effect among all four fractions was from the anthocyanin fractions. Both HT-29 and Caco-2 cell growth was significantly inhibited by >50% by the anthocyanin fractions at concentrations of 15-50 microg/mL. Anthocyanin fractions also resulted in 2-7 times increases in DNA fragmentation, indicating the induction of apoptosis. The effective dosage levels are close to the reported range of anthocyanin concentrations in rat plasma. These findings suggest that blueberry intake may reduce colon cancer risk.

PMID: 16131149 [PubMed - indexed for MEDLINE]