title: Tumor-suppressive activity of 1,25-dihydroxyvitamin D3 against kidney cancer cells via up-regulation of FOXO3.
abstract: 1,25-Dihydroxyvitamin D3 has been known to have the tumor-suppressive activity in various kinds of tumors. However, the exact effect and working mechanism of 1,25-dihydroxyvitamin D3 on the tumor-suppressive activity in human kidney cancer cells remains poorly understood. 1,25-Dihydroxyvitamin D3 has cytotoxicity to ACHN cells and inhibited ACHN cell proliferation compared to the vehicle control. 1,25-Dihydroxyvitamin D3 increased the expression of the cleaved PARP1, active Caspase3, Bax, and Bim but decreased the expression of Bcl2 in ACHN cells. Moreover, 1,25-dihydroxyvitamin D3 down-regulated the phosphorylated Akt and Erk which might lead to apoptosis through activation of FOXO3 in ACHN cells. Transfection of siRNA against FOXO3 attenuated the pro-apoptotic BimEL expression in ACHN cells treated with 1,25-dihydroxyvitamin D3. These results suggest that FOXO3 is involved in the apoptosis induced by 1,25-dihydroxyvitamin D3.
authors.affiliation: a Department of Genetic Engineering , Sungkyunkwan University , Suwon , Korea.
authors.forename: Jongsung
authors.initials: J
authors.lastname: Lee
authors.affiliation: b Department of Bio and Chemical Engineering , Hongik University , Sejong , Korea.
authors.forename: See-Hyoung
authors.initials: SH
authors.lastname: Park
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002117:Calcitriol / Q000494:pharmacology*; D002292:Carcinoma, Renal Cell / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D000071316:Forkhead Box Protein O3 / Q000378:metabolism*; D006801:Humans; D007680:Kidney Neoplasms / Q000473:pathology*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D000071316:Forkhead Box Protein O3; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D002117:Calcitriol
keywords: 1,25-dihydroxyvitamin D3; FOXO3; cancer; kidney; tumor-suppressive