In Vivo Inhibition of Growth of Human Tumor Lines by Flavonoid Fractions From Cranberry Extract

Abstract

Edible fruits and berries may serve as sources for novel anticancer agents, given that extracts of these foods have demonstrated cytotoxic activity against tumor cell lines. Semipurified, flavonoid-rich extracts of cranberry (Vaccinia macrocarpa) were shown previously to arrest proliferation of tumor cells and induce apoptosis. However, the ability of cranberry flavonoids to inhibit tumor growth in vivo has not been reported other than in a preliminary report. As model systems for testing this activity, human tumor cell lines representative of three malignancies were chosen: glioblastoma multiforme (U87), colon carcinoma (HT-29), and androgen-independent prostate carcinoma (DU145). A flavonoid-rich fraction 6 (Fr6) and a more purified proanthocyanidin (PAC)-rich fraction were isolated from cranberry presscake and whole cranberry, respectively, by column chromatography. Fr6 and PAC each significantly slowed the growth of explant tumors of U87 in vivo, and PAC inhibited growth of HT-29 and DU145 explants (P < 0.05), inducing complete regression of two DU145 tumor explants. Flow cytometric analyses of in vitro-treated U87 cells indicated that Fr6 and PAC could arrest cells in G1 phase of the cell cycle (P < 0.05) and also induce cell death within 24 to 48 h of exposure (P < 0.05). These results indicate the presence of a potential anticancer constituent in the flavonoid-containing fractions from cranberry extracts.

Anticancer Activity and Nutritional Value of Extracts of the Seed of Glinus lotoides

“…The dietary flavonoids possess antioxidative, anti-inflammatory, and possibly anticarcinogenic properties and are receiving increasing attention. Flavonoids have been demonstrated to induce cell death or cell cycle arrest depending on their type and concentration (18). Apigenin, a widely distributed plant flavonoid abundantly present in fruits and vegetables, is a free-radical scavenger that has been shown to possess anti-inflammatory and anticarcinogenic effects (41).…”

Morphometric abnormalities in spleen and kidney of the progeny of mice fed American cranberry extract (Vaccinium macrocarpon) during pregnancy and lactation

“…Quercetin is a major flavonoid in cranberry fruit (Choi et al 2001, Ferguson et al 2006. Characterization of an active subfraction of proanthocyanidins revealed the presence of dimers and oligomers of catechin-epicatechin, monomeric catechins, and quercetin glycosides (Neto 2007).…”

Cranberries and Cancer: An Update of Preclinical Studies Evaluating the Cancer Inhibitory Potential of Cranberry and Cranberry Derived Constituents

“…Bromodeoxyuridine (BrdU) incorporation assays as a measurement of cell proliferation inform how cranberry derived constituents modulate S-phase cell cycle kinetics. Esophagus CP-C C-PAC ↓ total reactive oxygen species [38] JHEsoAD1 C-PAC ↑ autophagy in acid-sensitive cells, pro-death [39,40] ↑ necrosis in acid-resistant cells [39] ↑ G 2 -M cell cycle arrest [39] ↑ total reactive oxygen species [38] ↑ hydrogen peroxide levels [38] ↓ cell viability [40,41] ↓ PI3K/AKT/mTOR signaling [39] OE33 C-PAC ↑ autophagy in acid-sensitive cells [39] ↑ low levels of apoptosis [39]↑ G 2 -M cell cycle arrest [39] ↓ cell proliferation [39] ↑ total reactive oxygen species [38] ↓ PI3K/AKT/mTOR signaling [39] OE19 C-PAC ↑ necrosis in acid-resistant cells [39] ↑ G 2 -M cell cycle arrest with significant S-phase delay [39] ↑ total reactive oxygen species [38] ↑ hydrogen peroxide levels [38] ↓ PI3K/AKT/mTOR signaling [39] ↓ cell viability [40,41] Glioblastoma SF295 UA ↓ cell density [29] U87 C-PAC ↑ apoptosis [36]; ↑ G 1 cell cycle arrest [36] ↓ cell viability [36] …”

“…↑ apoptosis [36]; ↑ G 1 cell cycle arrest [36] ↓ cell viability [28] Leukemia K562 C-PAC ↓ cell density [26] RPMI8226 UA ↓ cell density [29] Liver HepG2 CE ↑ reduced glutathione levels [22] ↓ glutathione peroxidase activity [22] ↓ lipid peroxidation [22] ↓ reactive oxygen species [22] …”

“…Cancer cell lines originating from the oral cavity are susceptible to reduced viability following treatment with cranberry extract (50.0-180.6 µg/mL), cranberry juice extract (150.0 µg/mL) and a total polyphenolic fraction (200.0 µg/mL) with cranberry extract (50.0 µg/mL) treatment of CAL27 cells having the lowest GI 50 [24,33,47]. Ten studies have documented the effectiveness of a cranberry extract, cranberry juice extract, a flavonoid rich extract and cranberry proanthocyanidins at significantly reducing the viability of prostate cancer cells [24][25][26]28,33,36,45,[50][51][52]. The most efficacious constituent appears to be a cranberry proanthocyanidin extract, which inhibits the viability of RWPE-1 and RWPE-2 prostate cancer cell lines with a GI 50 of approximately 6.5 µg/mL [33].…”