Inhibition of human colon cancer cell growth with β-sitosterol: Role of membrane lipid alterations

The present study was designed to examine the effect of β-sito8terol on the growth and membrane lipida of HT-29 cells. HT-29 cells were grown in the presence of either cholesterol or β-aitosterol at a concentration up to 16 μM in Dulbecco's MEM. Sterols were supplied ae cyclodextrin - sterol complex. Cell growth was followed by counting the number of cells in culture. At 8 μK, sterol significant growth reduction was observed with β-eitosterol as compared to cholesterol. The effect was more pronounced at 16 μM sterol in the media. At day 9, the growth of cells supplemented with β-sitoaterol was only 33% of these supplemented with cholesterol. The incorporation of β-sitosterol did not influence the membrane cholesterol/phoepholipid ratio as compared to doubling this ratio in the case of cholesterol supplementation. Supplementation with 16 μM sitosterol resulted in reducing membrane sphingomyelin concentration by 46% as compared to cholesterol. Supplementation with sitosterol resulted in a significant increase in membrane saturated atty acids. There was a 30% increase in total monunsaurated fatty acids with sitosterol supplementation in the Bphingomyelin but a 40% decreaae in the phosphatidylserine fraction. There was a significant increase in ω-3 fatty acids in both phosphatidylserine and phosphatidylinositol with sitosterol supplementation. These data suggest that the inhibition of tumor growth of HT-29 cells by β-sitosterol may be mediated through alterations in lipid composition of membranes since phoapholipids are involved in signal transduction. Supported by a grant from the Alien Foundation.