Silymarin is a naturally available bioflavonoid and is a strong antioxidant with a capacity to inhibit the formation of tumors in several cancer models. In the present study, we investigated whether dietary supplementation of silymarin has any role in lipid components, lipid-metabolizing enzymes, free fatty acid profile, and expression of cyclooxygenase-2 (COX-2) in N-nitrosodiethylamine (NDEA)-induced hepatocellular carcinoma in rats. NDEA-induced rats showed severe hyperlipidemia along with upregulated expression of COX-2 as revealed by western blotting and immunohistochemistry. Dietary silymarin supplementation attenuated this hyperlipidemia and downregulated the expression of COX-2. Thus we conclude that compounds like silymarin with potent hypolipidemic effect are strong candidates as chemopreventive agents for the treatment of liver cancer.

Our results demonstrate that silymarin treatment inhibited proliferation and induced apoptosis in the human hepatocellular carcinoma cell line HepG2.

Coumarin and its derivative 7-hydroxycoumarin (7-OHC) have antitumor and antimetastatic properties. The purpose of this study was to investigate the possible effects of these compounds on expression of the bcl-2 and Bax oncoproteins in two human lung cancer cell lines, A427 and Calu-1. The cells were cultured in vitro for 24 h in RPMI 1640 with 1.5% (v/v) ethanol, 1.0 mM ethanolic coumarin or 1.0 mM ethanolic 7-OHC. Viability was determined in each cell line by an MTT assay. Total protein was extracted from cell lysates and the bcl-2 and Bax oncoproteins were identified. Western blotting showed a decrease in bcl-2 and an increase in Bax in A427 cells cultured with coumarin or 7-OHC. Neither drug changed bcl-2 expression in Calu-1 cells compared to solvent controls, and Bax expression was only slightly increased by coumarin. We conclude that 7-OHC is a more potent inhibitor of cell proliferation than coumarin and has more marked effects on oncoprotein expression. Also, the A427 cell line was more sensitive to the drugs than Calu-1.

On the basis of previous conformational and configurational studies of 4-aryl-substituted cyclophosph(on)ates derived from d-xylofuranose derivatives, wherein it was proposed that the anomeric effect is involved in the spontaneous isomerization of the P atom and the C4 carbon, and consequently, this unusual behavior was associated with the cleavage of the HepDirect prodrugs. We synthesized an analogous series of 2-amino-2-oxo-1,3,2-dioxaphosphorinanes and performed a conformational and configurational analysis in solution and the solid state followed by an examination of their mutagenic activity. The results showed that the 2-amino-2-oxo-1,3,2-dioxaphosphorinanes with the largest mutagenic activity contain either a 4-methoxyphenyl or 4-fluorophenyl group at C4 carbon and presented a major chair conformation, which is prone to weaken the C4-O3 bond via the anomeric effect and facilitates the cleavage for the release of the biologically active metabolite.