Food Lipids: Chemistry, Nutrition, and Biotechnology

In contrast to the antioxidative properties of CLA, results from experiments
using human cancer cell lines suggested that CLA, because of its susceptibility to
oxidative damage, could behave as a prooxidant in cell culture systems. Moreover,
CLA may create an oxidatively stressed environment that is cytotoxic to cultured
cells (77,110). O’Shea et al. (110) used CLA dissolved in ethanol, which was added
to a human cell culture (MCF-7 breast cancer line and SW-480 colon cancer cell
line) media at concentrations of 0, 5, 10, 15, 20, and 30 ppm and incubated for 4,
8, and 12 days. The CLA treatment at 20 ppm increased lipid peroxidation and
induced the expression and activity of antioxidant enzymes (superoxide dismutase,
catalase, and glutathione peroxidase) in both cell lines. At 20 ppm, CLA also reduced
3 H-leucine incorporation into protein by 83–91% and 3 H-uridine and 3 H-thymidine
incorporation into RNA and DNA by 49–91% and 86–98%, respectively, compared
with untreated control cells. O’Shea et al. (111) showed that milk fat enriched with
CLA (primarily the triglyceride-bound c9,t11 isomer) induced the activities of superoxide
dismutase (SOD), catalase, and glutathione peroxidase (GPx) in MCF-7
human breast cancer cell cultures and inhibited the growth and proliferation of these
cells. Apparently, at least in part, the induced antioxidant enzyme system failed to
protect these cells from peroxidative cytotoxicity. The controversial effect of CLA
as an antioxidant or prooxidant agrees with previous knowledge that the balance
between antioxidant and prooxidant activity is known to be a complex function
dependent on the concentration of the testing material and oxygen partial pressure
(112).
Basu et al. (113,114) reported the investigations of the urinary levels of 8-iso-
PGF 2�, a major isoprostane, and 15-keto-dihydro-PGF 2�, a major metabolite of PGF 2�,
as indicators of nonenzymatic and enzymatic lipid peroxidation after dietary supplementation
of CLA in healthy and obese human subjects. A significant increase of
both 8-iso-PGF 2� and 15-ketodihydro-PGF 2� in urine was observed after 3 months
and 1 month of daily CLA intake (4.2 g/day).
B. Biochemical and Physiological Actions
Another potential action of CLA in preventing carcinogenesis is on DNA adduct
formation. For example, dietary CLA (1%, 0.5%, 0.1% diet) inhibited PhIP (a mammary
carcinogen)–DNA adduct formation in F344 rat liver and white blood cells in
a dose-dependent manner (102). Similar findings were also reported by Liew et al.
(58) that when F344 rats were given CLA (0.5% diet equivalent) by gavage, the
treatment significantly reduced IQ (2-amino-3-methylimidazo[4,5-f]quinoline)–DNA
adduct formation in the colon. Schut et al. (103) used the same rat model to study
CLA effects on both PhIP and IQ and found that CLA (0.1–1%) inhibited PhIP-
DNA adduct formation in mammary gland and the colon. It was concluded that CLA
could be a potential chemopreventive agent against PhIP- or IQ-induced tumors in
rodents.
The isomers of CLA might also initiate apoptosis to protect mammary gland
cells from chemically induced carcinogenesis. Ip et al. (60) showed in a primary
culture of rat normal mammary epithelial organoids (MEOs) that CLA (0–128 �M),
but not LA, inhibited growth of MEO which was further shown to be mediated by
a reduction in DNA synthesis and a stimulation of apoptosis. Ip et al. (115) showed
that CLA was able to increase chromatin condensation and to induce DNA laddering
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