γ-Tocopherol inhibits human prostate cancer cell proliferation by up-regulation of transglutaminase 2 and down-regulation of cyclins

• Published in: Amino acids 2013, Vol.44 (1), p.45-51
• Main Authors: Torricelli, P., Caraglia, M., Abbruzzese, A., Beninati, S.
• Format: Article
• Language: English
• Subjects: Activation; alpha-Tocopherol - pharmacology; Analytical Chemistry; Antineoplastic Agents - pharmacology; Biochemical Engineering; Biochemistry; Biomedical and Life Sciences; Cancer; Cell Cycle - drug effects; Cell Line, Tumor; Cell Proliferation - drug effects; Cyclin D1 - genetics; Cyclin D1 - metabolism; Cyclin E - genetics; Cyclin E - metabolism; Differentiation; DNA Replication - drug effects; Down-Regulation; Enzyme Induction - drug effects; Flow cytometry; gamma-Tocopherol - pharmacology; GTP-Binding Proteins; Human; Humans; Life Sciences; Male; Neurobiology; Original Article; Progressions; Prostate; Prostatic Neoplasms; Proteomics; Therapy; Transglutaminases - genetics; Transglutaminases - metabolism; Up-Regulation; Vitamins - pharmacology
• ISSN: 0939-4451; 1438-2199
• DOI: 10.1007/s00726-012-1278-y

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.