Vitamin E Isoforms Inhibit Cell Proliferation and Downregulate Homeobox Protein Expression in the Leukemic KG-1 Cells.

Vitamin E is a fat-soluble vitamin that exists in eight different isoforms: four tocopherols (alpha, beta-, gamma- and delta-), and four tocotrienols (also alpha-, beta-, gamma- and delta-). Studies are underway to determine whether vitamin E, through its ability to limit production of free radicals, might help prevent or delay the development of cancer. Other studies suggest that vitamin E may modulate signal transduction pathways to prevent or reverse the effects of cancer. In our study, we examined the effect of vitamin E isotypes on some gene products involved in acute leukemia such as HOXA9 (Homeobox A9), PBX1 (Pre-B cell leukemia transcription factor 1) and E2A-PBX1. HOXA9 is a transcription factor with a central role in both hemopoiesis and leukemia. A high level of HOXA9 is a characteristic feature of acute myeloid leukemia (AML) and may be sufficient to cause this disease. PBX1 is involved in a form of pre-B-cell acute lymphoblastic leukemia (B-ALL). E2A-PBX1 is a protein resulting from a chromosomal translocation t(1;19)(q23;p13.3) which involves PBX1 and E2A genes. E2A-PBX1 transforms cells by constitutively activating transcription of genes regulated by PBX1 or by other members of the PBX protein family. KG-1 cells were treated with 20 micromolar (μM) gamma tocotrienol (γT3) and delta tocotrienol (δT3) for 48 hours, and 50 μM gamma tocopherol (γT) and delta tocopherol (δT) for 72 hours. MTT Assays demonstrate 30% inhibition of cell proliferation using 50 μM γT after 72 hours, 60% inhibition of cell proliferation using 50 μM δT after 48 hours, 70% inhibition of cell proliferation using 25 μM γT3 after 48 hours, and 75% inhibition of cell proliferation using 25 μM δT3 after 48 hours. Western Blot analysis was performed on the cell lysates using HOXA9, PBX1 and E2A-PBX-1 antibodies. Our results showed that both δT and γT when used at a 50 μM concentration for 72 hours treatment, as well as δT3 and γT3 when used at a 20 μM concentration for 48 hours treatment, have a down regulatory effect on HOXA9, PBX1 and E2A-PBX-1 protein expression in the leukemic KG-1 cells. A down regulatory effect on cyclin D1 and cyclin D3 was also demonstrated.