Polyethylene glycol inhibits intestinal neoplasia and induces epithelial apoptosis in Apc(min) mice.


Efficacy of a safe and clinically utilized polyethylene glycol formulation (PEG-3350) to suppress intestinal tumors was investigated in the Apc(min) mouse-model of experimental carcinogenesis. Furthermore, based on our previous finding on the induction of apoptosis in HT-29 cells by PEG, we evaluated its ability to stimulate epithelial cell apoptosis in both Apc(min) mouse as well as AOM-treated rat as a potential molecular mechanism of chemoprevention. Twenty-two Apc(min) mice were randomized equally to PEG or vehicle (control) supplementation. Tumors were scored and uninvolved intestinal mucosal apoptosis was assayed using a modified terminal deoxynucleotidyl transferase-mediated nick end-labeling (TUNEL) assay and by immunohistochemical detection of cleaved caspase-3. Supplementation of Apc(min) mice with 10% PEG 3350 (in drinking water) resulted in a 48% (P<0.05) reduction in intestinal tumor burden and induced 2-3 fold increase in mucosal apoptosis. Dietary supplementation of polyethylene glycol (5%) also stimulated colonic mucosal apoptosis 4-5 fold in AOM-treated rats, the regimen that we previously reported to reduce tumor burden by 76% (P<0.05). In summary, we demonstrate, for the first time, that PEG does protect against Apc(min) mouse tumorigenesis. The correlation between pro-apoptotic actions and chemopreventive efficacy of PEG in these models strongly implicates induction of apoptosis as one of the impending mechanisms of chemoprevention.

  • Ansari S
  • Bissonnette M
  • DiBaise JK
  • Gulizia J
  • Hart J
  • Karolski WJ
  • Madugula M
  • Roy HK
  • Wali RK
PubMed ID
Appears In
Cancer Lett, 2004, 215 (1)