Chemopreventive effects of dietary cottonseed oil

描述(由申请人提供)： 棉酚(Gp)是棉籽中存在的一种天然多酚色素。 产品，如棉籽油(CSO)，供人类和 食品性动物。GP的抗癌活性有很好的文献记载 在我们的实验室和其他实验室的研究。 我们已发表的初步结果表明：(A)GP减少了原发肿瘤 荷瘤哥本哈根大鼠的生长和肺及淋巴结转移 Mat-LyLu Dunning前列腺癌细胞；(B)GP诱导的细胞周期停滞 PC-3细胞和培养的人BPH细胞与升高的转化生长因子-β有关；(C) GP抑制MAT-LyLu细胞的体外侵袭活性；(D)雏鸡 胚胎绒毛尿囊膜实验显示GP抑制血管生成； (E)从人肺转移瘤中分离到一种新的mat-lyLu亚系。 携带MAT-LyLu的哥本哈根大鼠(MLL细胞)表现出更大的侵袭性 Nm23转移抑制基因的能力和较低的mRNA水平；和(F)CSO 对PC-3细胞具有极强的抗增殖活性 体外培养。然而，通过消费摄入GP的潜在生物医学好处 还没有关于含有CSO的食品的报告。我们的目标是 评价摄入含CSO的试验性日粮对仔猪的影响 荷MAT-LyLu或MLL细胞的哥本哈根大鼠肿瘤生长和转移 洞察CSO作为饮食化学预防的潜在效用 或前列腺癌的治疗剂。这项研究的具体目的是 以：(1)确定是否摄入含CSO的试验性日粮 会预防和/或抑制哥本哈根大鼠肿瘤的生长和转移 承载MAT-LLU或MLL肿瘤：(2)确定是否消耗 含CSO饮食诱导的转化生长因子-I3和nm23表达水平升高 转移抑制基因，和/或减少微血管密度作为衡量 MAT-LyLu和MLL荷瘤哥本哈根原发肿瘤内血管生成的研究 (3)比较MAT-LyLu和新分离的MLL在体内的行为。 细胞与哥本哈根大鼠肿瘤生长和转移的关系；(4) 评估食用含CSO的有害物质的潜在毒性 节食。饲喂含有不同水平CSO的试验日粮 对雄性哥本哈根大鼠皮下植入MAT-LyLu或MLL 细胞。喂食开始的时间与日不同 植入。在研究过程中将监测肿瘤的生长情况。 肿瘤大小、肿瘤转化生长因子-β和nm23水平、血清睾酮水平、 转化生长因子-b蛋白和乳酸脱氢酶活性、肿瘤微血管密度和糖蛋白水平 收集的组织将被确定。我们建议的研究结果可能 确定可用于预防糖尿病的饮食成分 前列腺癌细胞的生长和转移。拟议的研究将作为 膳食CSO在未来临床试验中的临床前基础 预防和抑制人前列腺癌的生长和/或 转移。

DESCRIPTION (provided by applicant): 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.