Polyethylene glycol induces apoptosis in HT‐29 cells: potential mechanism for chemoprevention of colon cancer

Abstract

Recent experimental evidence suggests that polyethylene glycol (PEG) is a highly effective chemopreventive agent against colon cancer; however, the mechanism(s) remain largely unexplored. To further elucidate this issue, we evaluated the effect of PEG on two human colon cancer cell lines. PEG treatment resulted in a dose-and time-dependent reduction in cell number without alteration in markers of cell proliferation. However, there was a dramatic and specific, concentrationdependent induction of apoptosis, with 50 mM PEG rendering approximately half the cells apoptotic. This corresponded with a 17-fold induction in the expression of the pro-apoptotic protein, prostate apoptosis response-4. Our data suggest that induction of apoptosis may be responsible, at least in part, for the ability of PEG to prevent experimental colon cancer. ß 2001 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.

Chemoprevention of colon carcinogenesis by polyethylene glycol: suppression of epithelial proliferation via modulation of SNAIL/β-catenin signaling

“…Our results from the cell culture, in keeping with the study from Corpet's laboratory (26), indicate that PEG has a marked cytoprotective effect. Furthermore, antiproliferative effect of PEG complements its proapoptotic effect that we have previously reported in cell culture, azoxymethane-treated rat, and the MIN mouse (17,41).…”

“…Epidermal growth factor receptor is known to induce SNAIL (49). Another point that needs to be emphasized is that whereas our article focuses on proliferation, we have previously shown that PEG also induces apoptosis in animal models and cell culture (17,41). Clearly, both SNAIL and h-catenin have important effects on apoptosis.…”

Involvement of p21cip1/waf1 in the anti-proliferative effects of polyethylene glycol in colon carcinogenesis

“…In the studies on AOM-induced ACF suppression, the optimal formulation of PEG has been shown to be PEG-8000, though understanding its molecular targets may help redefine the specificity and effectiveness of other formulations. Previous reports on PEG's potential mechanism of action have suggested number of possibilities i.e., suppression of proliferation, induction of apoptosis, epitheliolysis (28,29). While these and other mechanisms are likely to contribute to the overall chemopreventive efficacy, the data supporting the importance of suppression of proliferation in chemoprevention is unequivocal.…”

“…These have been complemented by reports that PEG has inhibited proliferation in a wide variety of CRC cells lines (12,13,29) although, the mechanisms had remained largely unexplored. Thus, our data demonstrated that there was a striking inhibition of G1➝S phase progression suggesting that this was a key factor in the suppression of proliferation by PEG.…”

“…While our study does not preclude a role for the other modulators, we clearly show that p21 regulation appears to be important in the process. Finally, this study focuses exclusively on proliferation and it is obvious that PEG may also induce apoptosis (29). We did not explore the role of p21 in apoptosis although there is precedence to it.…”