Chemoprevention of familial adenomatous polyposis in Apc(Min/+) mice by phenethyl isothiocyanate (PEITC).
Phenethyl isothiocyanate (PEITC) is an isothiocyanate which is a major constituent of watercress and other cruciferous vegetables. Its chemopreventive potential has been previously shown in various rodent models of cancer. In this study, we investigated the chemopreventive efficacy of PEITC in the Apc(Min/+) mouse model. Apc(Min/+) mice were fed with diet supplemented with 0.05% of PEITC for 3-wk. Our results clearly demonstrated that Apc(Min/+) mice fed with PEITC supplemented diet developed significantly less (31.7% reduction) and smaller polyps in comparison to mice fed with the standard AIN-76A diet. Subsequent mechanistic study using Western blotting shows that inhibition of growth of adenomas by PEITC is associated with increase of apoptosis (cleaved-caspase-3, -caspase-7, and PARP). Treatments also led to the inhibition of cell cycle-related biomarkers such as the cyclins (D1, A, and E) and activation of p21. However, PEITC has no effect on the expression of p-Erk, p-JNK or p-p38. In conclusion, our results demonstrate that PEITC is a potent natural dietary compound for chemoprevention of gastrointestinal cancers. Its mechanism of actions may include induction of apoptosis and cell cycle arrest.
Khor
Tin Oo
TO
Center for Cancer Prevention Research, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
Cheung
William Ka Lung
WK
Prawan
Auemduan
A
Reddy
Bandaru S
BS
Kong
Ah-Ng Tony
AN
D011125:Adenomatous Polyposis Coli / Q000235:genetics / Q000517:prevention & control*; D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D018890:Chemoprevention; D019587:Dietary Supplements; D017491:Genes, APC / Q000502:physiology*; D007414:Intestinal Neoplasms / Q000235:genetics / Q000517:prevention & control*; D017879:Isothiocyanates / Q000627:therapeutic use*; D051379:Mice; D018345:Mice, Knockout; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism
D016588:Anticarcinogenic Agents; D017879:Isothiocyanates; C058305:phenethyl isothiocyanate; D020928:Mitogen-Activated Protein Kinases; D020169:Caspases