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

Hemant K. Roy, James Gulizia, John K. DiBaise, William J. Karolski, Sajid Ansari, Madhavi Madugula, John Hart, Marc Bissonnette, Ramesh K. Wali

Research output: Contribution to journalArticle

17 Scopus citations

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 languageEnglish (US)
Pages (from-to)35-42
Number of pages8
JournalCancer Letters
Volume215
Issue number1
DOIs
StatePublished - Nov 8 2004

Keywords

  • Aberrant crypt foci
  • Apcmin mouse
  • Apoptosis
  • Azoxymethane
  • Chemoprevention
  • Polyethylene glycol

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Roy, H. K., Gulizia, J., DiBaise, J. K., Karolski, W. J., Ansari, S., Madugula, M., Hart, J., Bissonnette, M., & Wali, R. K. (2004). Polyethylene glycol inhibits intestinal neoplasia and induces epithelial apoptosis in Apc min mice. Cancer Letters, 215(1), 35-42. https://doi.org/10.1016/j.canlet.2004.05.012