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.