American cranberry (Vaccinium macrocarpon) extract affects human prostate cancer cell growth via cell cycle arrest by modulating expression of cell cycle regulators

Abstract

Prostate cancer is one of the most common cancers in the world, and its prevalence is expected to increase appreciably in the coming decades. As such, more research is necessary to understand the etiology, progression and possible preventative measures to delay or to stop the development of this disease. Recently, there has been interest in examining the effects of whole extracts from commonly harvested crops on the behaviour and progression of cancer. Here, we describe the effects of whole cranberry extract (WCE) on the behaviour of DU145 human prostate cancer cells in vitro. Following treatment of DU145 human prostate cancer cells with 10, 25 and 50 μg ml⁻¹ of WCE, respectively for 6 h, WCE significantly decreased the cellular viability of DU145 cells. WCE also decreased the proportion of cells in the G2-M phase of the cell cycle and increased the proportion of cells in the G1 phase of the cell cycle following treatment of cells with 25 and 50 μg ml⁻¹ treatment of WCE for 6 h. These alterations in cell cycle were associated with changes in cell cycle regulatory proteins and other cell cycle associated proteins. WCE decreased the expression of CDK4, cyclin A, cyclin B1, cyclin D1 and cyclin E, and increased the expression of p27. Changes in p16(INK4a) and pRBp107 protein expression levels also were evident, however, the changes noted in p16(INK4a) and pRBp107 protein expression levels were not statistically significant. These findings demonstrate that phytochemical extracts from the American cranberry (Vaccinium macrocarpon) can affect the behaviour of human prostate cancer cells in vitro and further support the potential health benefits associated with cranberries.

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

“…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]. In contrast, prostate cancer cells are not particularly sensitive to inhibition by a flavonoid rich extract as the GI 50 concentration for DU-145 (234.0 µg/mL) cancer cells is comparatively 1.6-3.0 fold higher compared to the GI 50 for glioblastoma (77.0 µg/mL), melanoma (147.0 µg/mL) and breast (147.0-212.0 µg/mL) cancer cell lines [28]. Finally, two studies report cranberry and cranberry juice extract decrease the viability of stomach cancer cell lines AGS and SGC-7901 [25,53].…”

“…In comparison, a significant reduction in viability of esophageal adenocarcinoma and ovarian cancer cells is observed with 25.0-50.0 µg/mL and 50.0-200.0 µg/mL cranberry proanthocyanidins, respectively [40,41,45,48,49]. Reductions in viability of glioblastoma and melanoma cancer cell lines occur following treatment with a flavonoid rich extract, with the GI 50 for U87 glioblastoma cells about half of the GI 50 for SK-MEL5 melanoma cells after a 96h treatment [28]. A significant decrease in viability is observed for HepG2 liver cancer cells when treated for 4 days with a cranberry flavonoid glycoside extract (GI 50 = 49.2 µM), quercetin (GI 50 = 40.9 µM) or ursolic acid (GI 50 = 87.4 µM); where quercetin was the most effective of the three constituents [27].…”

“…The GI 50 concentration for ursolic acid is 1.2-11.2 µM in renal cancer cell lines RXF393, SN12C and TK-10, with similar results observed in breast (MCF-7; 1.4-1.9 µM), colon (HCT116; 1.5-3.5 µM) and lung (NCI-H322M; 1.2-9.8 µM) cancer cell lines when cell density is measured following a 48 h treatment [29,30]. The cell density of lung (NCI-H460; 20.0 µg/mL) and cervical (ME180; 30.0 µg/mL) cancer cell lines are similarly susceptible to cranberry proanthocyanidin treatment, while breast (MCF-7), melanoma (M-14), leukemia (K562) and prostate (PC3) cancer cell lines have GI 50 values greater than 70.0 µg/mL [26]. An organic soluble cranberry extract is effective at reducing cell density of two oral cancer cells lines, CAL27 and SCC25, at fairly similar GI 50 concentrations, 40.0 µg/mL and 70.0 µg/mL, respectively [46].…”

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

“…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].…”

“…The non-dialyzable material contains high molecular weight polyphenolic compounds, likely containing both proanthocyanidins and smaller quantities of anthocyanins [54]; however, structural characterization was not conducted due to the inability to hydrolyze the high molecular weight components into smaller oligomeric components for MALDI analysis [43]. 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].…”