The anti-tumour and anti-
cholesterol impacts of
tocotrienol-rich fraction (TRF) were investigated in rats treated with the chemical
carcinogen 7,12-dimethylbenz [alpha]
anthracene (DMBA), which is known to induce mammary
carcinogenesis and hypercholesterolaemia. DMBA administration to rats was associated with the appearance of multiple tumours on mammary glands after 6 months.
Alkaline phosphatase (ALP) and
glutathione-S-transferase (GST) are used as marker
enzymes to monitor the severity of
carcinogenesis. Although no tumours were visible on livers, hepatic ALP and GST activities of DMBA-treated rats were profoundly elevated in comparison to
enzyme activities of normal control rats. Feeding of TRF (10 mg/kg
body weight/day) for 6 months, isolated from
rice bran oil (RBO), to DMBA-administered rats, reduced the severity and extent of neoplastic transformation in the mammary glands. Similarly, plasma and mammary ALP activities increased during
carcinogenesis (95% and 43%, respectively), were significantly decreased in TRF-treated rats, whereas TRF mediated a further increase of 51% in hepatic ALP activity. TRF treatment to rats maintained low levels of GST activities in liver ( approximately 32%) and mammary glands ( approximately 21%), which is consistent with anti-carcinogenic properties of TRF. Administration of DMBA also caused a significant increase of 30% in plasma total
cholesterol and 111% in
LDL-cholesterol levels compared with normal control levels. Feeding of TRF to rats caused a significant decline of 30% in total
cholesterol and 67% in
LDL-cholesterol levels compared with the DMBA-administered rats. The experimental hypercholesterolaemia caused a significant increase in enzymatic activity (23%) and
protein mass (28%) of hepatic 3-hydroxy-3-methylglutaryl co-
enzyme A (
HMG-CoA) reductase. Consistent with TRF-mediated reduction in plasma
lipid levels, enzymatic activity and
protein mass of
HMG-CoA reductase was significantly reduced. These results indicate that TRF has potent anti-
cancer and anti-
cholesterol effects in rats.