Role of apoptosis, proliferating cell nuclear antigen and p53 protein in chemically induced colon cancer in rats fed corncob fiber treated with the fungus Pleurotus ostreatus.
The role of apoptosis, proliferative cell nuclear antigen (PCNA) and p53 protein in the preventive effects of dietary fiber treated with the fungus Pleurotus ostreatus on rat-colon tumorigenesis was studied. Tumors were induced by five subcutaneous injections of 1,2-dimethylhydrazine (DMH), 20 mg/kg rat, once a week. Rats were fed a semi-synthetic fiberfree diet (control) or a high-fiber diet (15%) derived from corncob treated or non-treated with the fungus. The rats we sacrificed 24 weeks after the first carcinogenic injection. The fungus treated corn-cob significantly decreased tumor incidence (to 26%) as compared to 44% and 57% in the other dietary groups. The apoptotic index (AI) significantly decreased in malignant tissue as compared to non-tumorous tissue. PCNA and cytoplasmic content of p53 protein exhibited an increasing trend in malignant tissue as compared to benign tissue (at 15% and 18%, respectively). The fungus-treated corncob significantly increased the content of p53 in the cell cytoplasm (to 33%) and its serum levels in tumor-bearing rats (to 38%). The cellular concentration of PCNA decreased to 61% in tumors obtained from rats fed the fungus-treated corncob as compared to controls. A high positive correlation was found between tumor grade and p53 protein in the serum (r = 0.97) or in the cell cytoplasm (r = 0.77) and between tumor grade and PCNA (r = 0.81). An inverse relationship was found between tumor grade and AI (r = -0.63). We found that 15% of corncob fiber alone seems not to be enough to prevent chemically induced tumorigenesis. The corncob fiber (15%) treated with the fungus had a significant protective effect against DMH-induced rat colon cancer, even at 15% and this effect was accompanied by the activation of some cellular mechanisms such as apoptosis, PCNA and p53 protein activation. Incubation of corncob with the fungus Pleurotus os, increased the dietary fiber content up to 78%. Thus corncob inhibits colon cancer development, and, therefore, may considered of potential use to the public.
Zusman
I
I
Laboratory of Teratology and Experimental Oncology, Koret School of Veterinary Medicine, Israel.
Reifen
R
R
Livni
O
O
Smirnoff
P
P
Gurevich
P
P
Sandler
B
B
Nyska
A
A
Gal
R
R
Tendler
Y
Y
Madar
Z
Z
D019813:1,2-Dimethylhydrazine; D000821:Animal Feed; D000818:Animals; D017209:Apoptosis; D002273:Carcinogens; D003106:Colon / Q000166:cytology / Q000187:drug effects / Q000473:pathology*; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D004043:Dietary Fiber; D004127:Dimethylhydrazines; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects / Q000473:pathology*; D008297:Male; D011124:Polyporaceae; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000097:blood; D003313:Zea mays
D002273:Carcinogens; D004043:Dietary Fiber; D004127:Dimethylhydrazines; D018809:Proliferating Cell Nuclear Antigen; D016159:Tumor Suppressor Protein p53; D019813:1,2-Dimethylhydrazine