title: γ-Tocopherol inhibits human prostate cancer cell proliferation by up-regulation of transglutaminase 2 and down-regulation of cyclins.
abstract: To establish a system to study differentiation therapy drugs, we used the androgen-independent human prostate PC-3 tumor cell line as a target and α- and γ-tocopherol as inducers. Effects of α- and γ-tocopherol on the cell cycle, proliferation and differentiation, were examined. A more significant growth inhibition activity for γ- than for α-tocopherol was observed. Flow cytometry analysis of α- and γ-tocopherol-treated prostate carcinoma PC3 cells showed decreased progression into the S-phase. This effect, particularly evident for γ-tocopherol, was associated with an up-regulation and increased activity of transglutaminase 2 (TG2), a reduced DNA synthesis and a remarkable decreased levels of cyclin D1 and cyclin E. Activation of TG2 suggests that γ-tocopherol has an evident differentiative capacity on PC3 cells, leading to an increased expression of TG2, and reduced cyclin D1 and cyclin E levels, affecting cell cycle progression. It is feasible that up-regulation and activation of TG2, associated with a reduced proliferation, are parts of a large-scale reprogramming that can attenuate the malignant phenotype of PC3 cells in vitro. These data suggest further investigation on the potential use of this γ-form of vitamin E as a differentiative agent, in combination with the common cytotoxic treatments for prostate cancer therapy.
authors.affiliation: Department SPES, University of Molise, Campobasso, Italy. xenografted@gmail.com
authors.forename: P
authors.initials: P
authors.lastname: Torricelli
authors.forename: M
authors.initials: M
authors.lastname: Caraglia
authors.forename: A
authors.initials: A
authors.lastname: Abbruzzese
authors.forename: S
authors.initials: S
authors.lastname: Beninati
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D019938:Cyclin D1 / Q000235:genetics* / Q000378:metabolism; D019927:Cyclin E / Q000235:genetics* / Q000378:metabolism; D004261:DNA Replication / Q000187:drug effects; D015536:Down-Regulation; D004790:Enzyme Induction / Q000187:drug effects; D019204:GTP-Binding Proteins; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation; D014815:Vitamins / Q000494:pharmacology; D024502:alpha-Tocopherol / Q000494:pharmacology; D024504:gamma-Tocopherol / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; C530104:CCND1 protein, human; D019927:Cyclin E; D014815:Vitamins; D019938:Cyclin D1; D024504:gamma-Tocopherol; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins; D024502:alpha-Tocopherol