In VitroAnticancer Activity of Fruit Extracts fromVacciniumSpecies

Abstract

Fruit extracts of four Vaccinium species (lowbush blueberry, bilberry, cranberry, and lingonberry) were screened for anticarcinogenic compounds by a combination of fractionation and in vitro testing of their ability to induce the Phase II xenobiotic detoxification enzyme quinone reductase (QR) and to inhibit the induction of ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine synthesis, by the tumor promoter phorbol 12-myristate 13-acetate (TPA). The crude extracts, anthocyanin and proanthocyanidin fractions were not highly active in QR induction whereas the ethyl acetate extracts were active QR inducers. The concentrations required to double QR activity (designated CDqr) for the ethyl acetate extracts of lowbush blueberry, cranberry, lingonberry, and bilberry were 4.2, 3.7, 1.3, and 1.0 microgram tannic acid equivalents (TAE), respectively, Further fractionation of the bilberry ethyl acetate extract revealed that the majority of inducer potency was contained in a hexane/chloroform subfraction (CDqr = 0.07 microgram TAE). In contrast to their effects on QR, crude extracts of lowbush blueberry, cranberry, and lingonberry were active inhibitors of ODC activity. The concentrations of these crude extracts needed to inhibit ODC activity by 50% (designated IC50) were 8.0, 7.0, and 9.0 micrograms TAE, respectively. The greatest activity in these extracts appeared to be contained in the polymeric proanthocyanidin fractions of the lowbush blueberry, cranberry, and lingonberry fruits (IC50 = 3.0, 6.0, and 5.0 micrograms TAE, respectively). The anthocyanidin and ethyl acetate extracts of the four Vaccinium species were either inactive or relatively weak inhibitors of ODC activity. Thus, components of the hexane/chloroform fraction of bilberry and of the proanthocyanidin fraction of lowbush blueberry, cranberry, and lingonberry exhibit potential anticarcinogenic activity as evaluated by in vitro screening tests.

Anthocyanins and Flavonoids of Vaccinium L.

“…The most striking antioxidant activity is cyaniding 3-galactose. DPPH assays showed that it was more effevtive than flavonol glycoside and the standards in scavenging free radicals, with an EC50 of 7.7 M compared to 17.3 M for myricetin 3-arabinoside and 30 M for trolox standard [4,130,131] Increased plasma antioxidant status, protected RBC against hemolysis [126,132] Showed protective effects on PC12 cells damage and chronic diseases associated with oxidative stress [133] Showed neuro and mitochondrio-protective effect [134] Antioxidant Activities Showed antioxidative activity under the used assay conditions towards prevention of oxidative DNA damage [135] Inhibited proliferation of MCF-7, MDA-MB-231 and MDA-MB-435 breast cancer cells [4,8,126,127] Inhibited the induction of ornithine decarboxylase, an enzyme involved in tumor proliferation, and induce quinine reductase, an enzyme that can inactivate certain carcinogens [136] Exhibited the human colon tumor cell lines Caco-2, HT-116, and HT-29 [10,137,138] Exhibited the anticancer effects on DLD-1 and COLO205 cells [139] Inhibited matrix metalloproteinase activity in DU145 human prostate cancer cells [140] Exhibition of anticancer capability in human lung and leukemia cells [105] Modulated the expression of cyclooxygenase-2 (COX-2) and I B in human colon cancer cells [141] Cytotoxicities Inhibitory effect on activator protein-1, nuclear factor-B, and mitogen-activated protein kinases activation [105,142] Prevented the urinary tract infections [143] Showed potential inhibitory effect against bacteria involved in dental caries and periodontal diseases [147,148] Exhibited potent biological activity by inhibiting adherence of uropathogenic isolates of P-fimbriated Escherichia coli bacteria to cellular surfaces containing -Gal(1 4)--Gal receptor sequences similar to those on epithelial cells in the urinary tract [149,150] Antimicrobial Activities…”

Expression of Genes Involved in Anthocyanin Biosynthesis in Relation to Anthocyanin, Proanthocyanidin, and Flavonol Levels during Bilberry Fruit Development

“…The content and composition of anthocyanins in bilberries, as well as in blueberries, has been determined earlier by Suomalainen and Keränen (1961), Martinelli et al (1986), and Wang et al (2000). Several studies have also been done on the bioactive properties of bilberries and blueberries (Bomser et al, 1996;Kalt and Dufour, 1997;Youdim et al, 2000), especially concerning the antioxidant activity of their anthocyanin fractions (Prior et al, 1998;Smith et al, 2000;Ehlenfeldt and Prior, 2001). However, to our knowledge, there are no published studies on flavonoid biosynthesis in blueberries with particular regard to the expression of genes in the phenyl propanoid pathway.…”

Complete Assignment of Bilberry (Vaccinium myrtillus L.) Anthocyanins Separated by Capillary Zone Electrophoresis

“…Anthocyanin, a reddish plant pigment, is a kind of flavonoid distributed widely in colored fruits and vegetables, including eggplants, 4) black currants, 5) grapes 6) and blueberries. 7,8) As with other flavonoids, the phytoceutical significance of anthocyanins has been discussed in relation to a wide range of physiological functions such as vision improvement, 9,10) anticancer activity, 11,12) and antioxidant activity. [13][14][15][16][17] Capillary electrophoresis (CE) has been successfully used in addition to HPLC to analyze flavonoids.…”