Abstract
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.
Original language | English (US) |
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Pages (from-to) | 35-42 |
Number of pages | 8 |
Journal | Cancer Letters |
Volume | 215 |
Issue number | 1 |
DOIs | |
State | Published - Nov 8 2004 |
Keywords
- Aberrant crypt foci
- Apcmin mouse
- Apoptosis
- Azoxymethane
- Chemoprevention
- Polyethylene glycol
ASJC Scopus subject areas
- Oncology
- Cancer Research