Phenolic Compounds from Blueberries Can Inhibit Colon Cancer Cell Proliferation and Induce Apoptosis

Abstract

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.

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…”

“…were found to induce apoptosis in cancer cells and to inhibit human leukemia [4][5][6][7] and breast [5,8], colon [4-7, 9, 10], lung [7], and prostate [5,11,12] cancer cells in vitro. Vaccinium has been an important source of food and pharmaceutical ingredients coupled with have high antioxidant potential [10,13,14]. The berries of many Vaccinium species are harvested for household consumption and commercial sale, particularly of bilberry (V. mytillus L.) [6,9], rabbiteye blueberry [10], lowbush blueberry (V. angustifolium Aiton) [11,12], cranberry (V. macrocarpon Aiton) [4,5,7], and highbush cultivated blueberry (V. corymbosum L.) [10,15].…”

“…Vaccinium has been an important source of food and pharmaceutical ingredients coupled with have high antioxidant potential [10,13,14]. The berries of many Vaccinium species are harvested for household consumption and commercial sale, particularly of bilberry (V. mytillus L.) [6,9], rabbiteye blueberry [10], lowbush blueberry (V. angustifolium Aiton) [11,12], cranberry (V. macrocarpon Aiton) [4,5,7], and highbush cultivated blueberry (V. corymbosum L.) [10,15]. Today, numerous Vaccinium berry and leaf extract products have been developed as dietary supplements.…”

Interaction between the Microbiome and Diet: The Hologenome Concept

“…These include such foods as pomegranate, blueberries, green tea, salmon, broccoli, garlic and gugi berries. Though the term "superfood" is considered to be more of a marketing term, professionals admit that these types of foods are nutraceutical-rich and have been shown to be healthy and disease preventing in animal trials [92,93] as well as some human clinical trials [94][95][96]. Many of the nutraceuticals contained in the superfoods are broken down in the human gut by the microbiota and this transformation often turns them into physiologically active materials.…”

Compostos bioativos de cultivares brasileiras de morango (Fragaria x ananassa Duch.): caracterização e estudo da biodisponibilidade dos derivados de ácido elágico

“…Alguns estudos relatam que embora as antocianinas estejam presentes em maiores concentrações, esses compostos são menos efetivos do que os elagitaninos (ROSS et al, 2007). No entanto, Yi et al (2005) analisaram frações ricas em antocianinas de mirtilo e esses compostos foram relatados como sendo os responsáveis pelo efeito antiproliferativo em linhagens celulares de câncer de cólon. Malik et al (2005) avaliaram o efeito in vitro e in vivo do suco de romã na inibição do crescimento de células humanas de carcinoma de próstata.…”