Cytostatic effect of polyethylene glycol on human colonic adenocarcinoma cells

Polyethylene glycol (PEG 8000) is a potent cancer chemopreventive agent. Th is osmotic laxative polymer markedly suppresses colon cancer in rats. To ex plain the mechanism, we have tested the in vitro effect of PEG on four huma n cell lines. Two poorly differentiated adenocarcinoma lines (HT29 and COLO 205), a fetal mucosa line (FHC) and a differentiated line (post-confluent C aco-2) were incubated with various PEG concentrations for 2-5 days. Results show that PEG markedly and dose dependently inhibited HT29 and COLO205 cel l growth. This cytostatic effect was associated with a blocking of the cell cycle in G0/G1 phase. In addition, PEG decreased the viability of HT29 and COLO205 adenocarcinoma cells. in contrast, post confluent intestinal-like Caco-2 cells and normal FHC cells were, respectively, not or little affecte d by PEG. Moreover, the lactate concentration increased twofold in the medi um of PEG-treated HT29 cells compared with untreated cells. Microscopic obs ervations showed that PEG induced cell shrinking, membrane blebbing and the condensation of nuclear chromatin, However, because no DNA ladder and no a nnexin staining were detected, we presume that PEG did not induce apoptosis , PEG increased the osmotic pressure of the culture medium. Hyperosmotic me dia with added NaCl or sorbitol also inhibited HT29 cell growth, and increa sed lactate release. These results suggest that PEG may be selectively cyto static for proliferating cancer cells. This growth inhibition may be due to the high osmotic pressure induced by PEG in vitro. Because the osmotic pre ssure is high in feces of PEG-fed rats, it may explain the suppression of c olon carcinogenesis by PEG. (C) 2001 Wiley-Liss, Inc.