Abstract. Clinical familial adenomatous polyposis (FAP) syndrome represents a high risk pre-invasive precursor for colon cancer, and is characterized by germ line mutation in the adenomatous polyposis coli (APC) tumor suppressor gene. Cellular models with relevant genetic and biological characteristics should provide important mechanistic leads for predisposition and preventive intervention. Cloned colon epithelial cell line from the Apc 850 Min /+ mouse represented a model for FAP. Cell cycle progression, cellular apoptosis and anchorage-independent growth represented the biomarkers for carcinogenic risk. The Apc mutant 850Min COL-Cl 1 cells exhibited decreased G 0 /G 1 :S+G 2 /M ratio, increased S+G 2 /M: subG 0 ratio, and increased anchorage-independent colony formation, indicating loss of homeostatic growth control and gain of anchorage-independent growth. Growth of these cells in serum-depleted medium was promoted by mitogenic insulin and epidermal growth factor, and inhibited by antimitogenic transforming growth factor-ß 1 and dexamethasone. Treatment with low dose combinations of synthetic enzyme inhibitor difluoro methylornithine (DFMO), synthetic nonsteroidal anti-inflammatory drug sulindac (SUL), and naturally occurring epigallocatechin gallate (EGCG), and eicosapentaenoic acid (EPA) produced cytostatic growth arrest and inhibited anchorage-independent colony formation. These data identify a novel cell culture model and validate a mechanism-based approach to prioritize combinations of effective chemopreventive compounds for prevention/therapy of colon cancer.
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