Lovastatin, delta-tocotrienol and genistein supress the proliferation of human Caco-2 colon carcinoma cells

The tumor-suppressive activity of three agents, lovastatin, delta-tocotrienol and genistein, traces to the agent-mediated suppression of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase activity the consequent depletion of growth-related intermediates. Lovastatin competitively inhibits reductase. delta-Tocotrienol post-transcriptionally down-regulates reductase. Genistem suppresses the transcription of reductase. Human Caco-2 colon carcinoma cells were cultured in growth media supplemented with various concentrations of lovastatin, delta-tocotrienol, and genistein at 37°C in a humidified atmosphere of 5% CO2 for 72 h. Cell proliferation was determined with manual counting. Each agent induced dose-dependent inhibition of cell proliferation. When individually applied, lovastatin (14 mumol/L), delta-tocotrienol (6 mumol/L) and genistien (12.5 mumol/L) suppressed Caco-2 cell proliferation by 17%, 4%, and 23%, respectively. A blend of all agents suppressed proliferation by 64%, exceeding the sum of individual impacts. Concomitant application of all three reductase suppressors may potentiate the tumor-suppressive activity of individual agents.