Dr. Weeks Comment: Once again Corrective Cancer Care™ is vindicated – anti-inflammatory agents are the future of cancer care. Choose the safest and most effective route – the anti-inflammatory diet bolstered by anti-inflammatory whole crushed organic, non-GMO seeds.
Anti”‘inflammatory drug resistance selects putative cancer stem cells in a cellular model for genetically predisposed colon cancer
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- Published online on: October 6, 2017 https://doi.org/10.3892/ol.2017.7147
Mutations in the adenomatous polyposis coli (Apc) tumor suppressor gene represent the primary genetic defect in colon carcinogenesis. Apc+/”‘ mouse models exhibit pre”‘invasive small intestinal adenomas. Cell culture models exhibiting Apc defects in the colon and quantifiable cancer risk provide a novel clinically relevant approach. The tumor”‘derived Apc”‘/”‘ colonic epithelial cell line 1638N COL”‘Pr1 represented the experimental model. The anti”‘inflammatory drugs sulindac (SUL) and celecoxib (CLX) represented the test compounds. Compared with non”‘tumorigenic Apc+/+ C57COL cells, the Apc+/”‘ 1638N COL cells and Apc”‘/”‘ 1638N COL”‘Pr1 cells exhibited progressive loss of homeostatic growth control. Compared with Apc+/”‘ cells, Apc”‘/”‘ cells displayed increased expression of biomarkers specific for hyper”‘proliferation. Treatment of Apc”‘/”‘ cells with SUL and CLX resulted in inhibition of anchorage”‘independent colony formation in vitro, which is indicative of reduced cancer risk in vivo. Mechanistically, SUL and CLX suppressed the expression of the Apc target genes Î²”‘catenin, cyclin D1, c”‘Myc and cyclooxygenase”‘2. Long”‘term treatment with high concentrations of SUL and CLX led to the selection of hyper”‘proliferative drug”‘resistant phenotypes. The Apc”‘/”‘ SUL”‘resistant phenotype displayed spheroid formation and enhanced the expression of the stem cell”‘specific molecular markers CD44, CD133 and c”‘Myc. These data demonstrated the growth”‘inhibitory efficacy of SUL and CLX and indicated that drug resistance leads to the selection of a putative cancer stem cell phenotype. The study outcome validates a stem cell”‘targeted mechanistic approach to identify testable alternative leads for chemotherapy-resistant colon cancer.