BETA-SITOSTEROL INHIBITS HT-29 HUMAN COLON-CANCER CELL-GROWTH AND ALTERS MEMBRANE-LIPIDS

The purpose of the present study was to examine the effect of beta-sit osterol, the main dietary phytosterol on the growth of HT-29 cells, a human colon cancer cell line. In addition, the incorporation of this p hytosterol into cellular membranes and how this might influence the li pid composition of the membranes were investigated. Tumor cells were g rown in DMEM containing 10% FBS and supplemented with sterols (cholest erol or beta-sitosterol) at final concentrations up to 16 mu M. The st erols were supplied to the media in the form of sterol cyclodextrin co mplexes. The cyclodextrin used was 2-hydroxypropyl-beta-cyclodextrin. The sterol to cyclodextrin molar ratio was maintained at 1:300. The st udy indicated that 8 and 16 mu M beta-sitosterol were effective at cel growth inhibition as compared to cholesterol or to the control (no st erol supplementation). After supplementation with 16 mu M beta-sitoste rol for 9 days, cell growth was only one-third that of cells supplemen ted with equimolar concentration of cholesterol. No effect was observe d on total membrane phospholipid concentration. At 16 mu M beta-sitost erol supplementation, membrane cholesterol was reduced by 26%. Cholest erol supplementation resulted in a significant increase in the cholest erol/phospholipid ratio compared to either beta-sitosterol supplemente d cells or controls. There was a 50% reduction in membrane sphingomyel in (SM) of cells grown in 16 mu M beta-sitosterol. Additional changes were observed in the fatty acid composition of minor phospholipids of beta-sitosterol supplemented cells, such as SM, phosphatidylserine (PS ), and phosphatidylinositol (PI). Only in the case of PI, was there an effect of these fatty acid changes on the unsaturation index, beta-si tosterol incorporation resulted in an increase in the U.I. It is possi ble that the observed growth inhibition by beta-sitosterol may be medi ated through the influence of signal transduction pathways that involv e membrane phospholipids.