title: Phosphatidylinositol 3-kinase mediates the ability of retinol to decrease colorectal cancer cell invasion.
abstract: Previously, we showed that retinol (vitamin A) decreased both colorectal cancer cell invasion and phosphatidylinositol 3-kinase (PI3K) activity through a retinoic acid receptor-independent mechanism. Here, we determined if these phenomena were related by using parental HCT-116 cells that harbor 1 allele of wild-type PI3K and 1 allele of constitutively active (ca) PI3K and 2 mutant HCT-116 cell lines homozygous for caPI3K. In vitro, treatment of parental HCT-116 cells with 10 μM retinol reduced cell invasion whereas treatment of mutant HCT-116 cell lines with retinol did not. Treatment with 10 μM retinol also decreased the activity of matrixmetalloproteinase-9 and increased tissue inhibitor of matrixmetalloproteinase-I levels in parental, but not mutant, HCT-116 cells. Finally, parental or mutant cells were intrasplenically injected into athymic mice consuming diets with or without supplemental vitamin A. As expected, vitamin A supplementation tended (P = 0.18) to reduce the incidence of metastases in mice injected with the parental cell line and consuming the supplemented diet. In contrast, metastatic incidence was not affected (P = 1.00) by vitamin A supplementation in mice injected with mutant cells. These data indicate that the capacity of retinol to inhibit PI3K activity confers its ability to decrease colorectal cancer metastasis.
authors.affiliation: a School of Family and Consumer Sciences, Nutrition and Foods Program , Texas State University-San Marcos , San Marcos , Texas , USA.
authors.forename: Jennifer N Griffin
authors.initials: JN
authors.lastname: Lengyel
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Park
authors.forename: Anna R
authors.initials: AR
authors.lastname: Brunson
authors.forename: Daniel
authors.initials: D
authors.lastname: Pinali
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Lane
mesh_terms: D000483:Alleles; D000818:Animals; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D005260:Female; D045325:HCT116 Cells; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009362:Neoplasm Metastasis / Q000517:prevention & control; D058539:Phosphatidylinositol 3-Kinase / Q000235:genetics* / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D014801:Vitamin A / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000081082:Phosphoinositide-3 Kinase Inhibitors; C560825:Timp1 protein, mouse; D019715:Tissue Inhibitor of Metalloproteinase-1; D014801:Vitamin A; D058539:Phosphatidylinositol 3-Kinase; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9