Gossypol (GP) is a natural polyphenolic pigment present in cottonseed products, such as cottonseed oil (CSO), that are consumed by humans and food-producing animals. The anticancer activities of GP are well-documented by research in our laboratory and others. Our published and preliminary results reveal: (a) GP reduced primary tumor growth and metastases to lungs and lymph nodes in Copenhagen rats bearing MAT-LyLu Dunning prostate cancer cells; (b) GP-induced cell cycle arrest in PC-3 cells and cultured human BPH cells is associated with elevated TGF-B; (c) GP inhibited the in vitro invasive activity of MAT-LyLu cells; (d) the chick embryo chorioallantoic membrane assay suggested that GP inhibits angiogenesis; (e) a novel MAT-LyLu subline has been isolated from the metastasized lungs of MAT-LyLu-bearing Copenhagen rats (MLL cells) which exhibit greater invasive ability and lower mRNA levels of nm23 metastasis suppressor gene; and (f) CSO possesses extremely potent antiproliferative activity against PC-3 cells in vitro. However, the potential biomedical benefits of GP intake via consumption of CSO-containing food products has not been reported. Our objective is to evaluate the effect of the consumption of CSO-containing experimental diets on tumor growth and metastasis in Copenhagen rats bearing MAT-LyLu or MLL cells to gain insight into the potential utility of CSO as a dietary chemopreventive or therapeutic agent for prostate cancer.
The specific aims of the study are to: (1) determine whether consumption of CSO-containing experimental diets will prevent and/or inhibit tumor growth and metastasis in Copenhagen rats bearing MAT-LyLu or MLL tumors: (2) determine whether consumption of CSO-containing diets induces elevates expression levels of TGF-I3 and nm23 metastasis suppressor gene, and/or reduces microvessel density as a measure of angiogenesis within primary tumors of MAT-LyLu- and MLL-bearing Copenhagen rats; (3) compare the in vivo behaviors of MAT-LyLu and the newly isolated MLL cells with respect to tumor growth and metastasis in Copenhagen rats; and (4) evaluate the potential toxicity resulting from consumption of CSO-containing diets. Experimental diets formulated with different levels of CSO will be fed to male Copenhagen rats bearing subcutaneous implants of MAT-LyLu or MLL cells. Feeding will begin at different times relative to the day of implantation. Tumor growth will be monitored during the course of the study. Tumor size, tumor levels of TGF-P and nm23, serum levels of testosterone, TGF-b protein and LDH activity, tumor microvessel density, and GP levels in collected tissues will be determined. The findings of our proposed study may identify a dietary component that can be exploited for the prevention of prostate cancer cell growth and metastasis. The proposed study will serve as a preclinical basis for future clinical trials of the utility of dietary CSO for the prevention and inhibition of human prostate cancer growth and/or metastasis.
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