Authors
So FV. Guthrie N. Chambers AF. Moussa M. Carroll KK.
Institution
Department of Pharmacology and Toxicology, University of Western Ontario,
London, Canada.
Title
Inhibition of human breast
cancer cell proliferation and delay of mammary tumorigenesis
by flavonoids and citrus juices.
Source
Nutrition & Cancer. 26(2):167-81, 1996.
Abstract
Two citrus flavonoids, hesperetin and naringenin, found in oranges and
grapefruit, respectively, and four noncitrus flavonoids, baicalein, galangin,
genistein, and quercetin, were tested singly and in one-to-one combinations
for their effects on proliferation and growth of a human
breast carcinoma cell line, MDA-MB-435. The concentration at
which cell proliferation was inhibited by 50% (IC50), based on incorporation
of [3H]thymidine, varied from 5.9 to 140 micrograms/ml for the single
flavonoids, with the most potent being baicalein. IC50 values for the
one-to-one combinations ranged from 4.7 micrograms/ml (quercetin +
hesperetin, quercetin + naringenin) to 22.5 micrograms/ml (naringenin +
hesperetin). All the flavonoids showed low cytotoxicity (> 500 micrograms/ml
for 50% cell death). Naringenin is present in grapefruit mainly as its
glycosylated form, naringin. These compounds, as well as grapefruit and
orange juice concentrates, were tested for their ability to inhibit
development of mammary tumors induced by 7,12-dimethylbenz[a]anthracene
(DMBA) in female Sprague-Dawley rats. Two experiments were conducted in which
groups of 21 rats were fed a semipurified diet containing 5% corn oil and
were given a 5-mg dose of DMBA intragastrically at approximately 50 days of
age while in diestrus. One week later, individual groups were given
double-strength grapefruit juice or orange juice or fed naringin or
naringenin at levels comparable to that provided by the grapefruit juice; in
the second experiment, the rats were fed a semipurified diet containing 20%
corn oil at that time. As expected, rats fed the high-fat diet developed more
tumors than rats fed the low-fat diet, but in both experiments tumor
development was delayed in the groups given orange juice or fed the
naringin-supplemented diet compared with the other three groups. Although
tumor incidence and tumor burden (grams of tumor/rat) were somewhat variable
in the different groups, rats given orange juice had a smaller tumor burden
than controls, although they grew better than any of the other groups. These
experiments provide evidence of anticancer properties of
orange juice and indicate that citrus flavonoids are effective inhibitors of
human breast cancer cell
proliferation in vitro, especially when paired with quercetin, which is
widely distributed in other foods.