In light of the continuing need for effective anticancer agents, and the association of fruit and vegetable consumption with reduced cancer risk, edible plants are increasingly being considered as sources of
anticancer drugs. Cranberry presscake (the material remaining after squeezing juice from the berries), when fed to mice bearing human breast tumor MDA-MB-435 cells, was shown previously to decrease the growth and
metastasis of tumors. Therefore, further studies were undertaken to isolate the components of cranberry that
contributed to this anticancer activity, and determine the mechanisms by which they inhibited proliferation. Using
standard chromatographic techniques, a warm-water extract of cranberry presscake was fractionated, and an
acidified methanol eluate (Fraction 6, or Fr6) containing flavonoids demonstrated antiproliferative activity. The
extract inhibited proliferation of 8 human tumor cell lines of multiple origins. The androgen-dependent prostate cell
line LNCaP was the most sensitive of those tested (10 mg/L Fr6 inhibited its growth by 50%), and the estrogen independent breast line MDA-MB-435 and the androgen-independent prostate line DU145 were the least sensitive
(250 mg/L Fr6 inhibited their growth by 50%). Other human tumor lines originating from breast (MCF-7), skin
(SK-MEL-5), colon (HT-29), lung (DMS114), and brain (U87) had intermediate sensitivity to Fr6. Using flow
cytometric analyses of DNA distribution (cell cycle) and annexin V-positivity (apoptosis), Fr6 was shown in
MDA-MB-435 cells to block cell cycle progression (P 0.05) and induce cells to undergo apoptosis (P 0.05) in
a dose-dependent manner. Fr6 is potentially a source of a novel anticancer agent.