Growth-inhibitory effects of vitamin E succinate on retrovirus-transformed tumor cells in vitro.
Vitamin E succinate inhibited proliferation of C4#1 cells, an established avian retrovirus [reticuloendotheliosis virus (REV)]-transformed immature lymphoid tumor cell line, in a dose-dependent manner. The cytostatic effects of vitamin E succinate were reversible in that treated cells regained their ability to divide after vitamin E succinate removal. Possible mechanism(s) for the antiproliferative actions of vitamin E succinate were investigated. Analyses of C4#1 cell surface membrane antigen profiles and morphology indicated that vitamin E succinate was not inducing differentiation of the tumor cells to a more mature, differentiated, nonproliferative state. Five antioxidants, including a synthetic analogue of vitamin E, Trolox, as well as the active vitamin form, DL-alpha-tocopherol, were incapable of inhibiting C4#1 tumor cell growth, indicating that a mechanism of action other than or in addition to functions as an antioxidant may be operating. Cell cycle analyses suggested that C4#1 tumor cells treated with vitamin E succinate were blocked in the G0G1/early S phases of the cell cycle. Tumor growth arrested by vitamin E succinate did not affect the expression of the REV-encoded oncogene, v-rel, at either the RNA or protein level. These studies demonstrated that vitamin E, in the form of vitamin E succinate, inhibited the growth of retrovirus-transformed tumor cells in vitro and suggested that the antiproliferative effects of vitamin E succinate did not involve antioxidant properties but rather, as yet, unidentified mechanisms leading to cell cycle blockage.
Kline
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K
Division of Nutrition, University of Texas, Austin 78712.
Cochran
G S
GS
Sanders
B G
BG
D000975:Antioxidants / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects*; D002472:Cell Transformation, Viral; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D012190:Retroviridae; D015682:Retroviridae Proteins, Oncogenic / Q000187:drug effects*; D024505:Tocopherols; D014407:Tumor Cells, Cultured / Q000187:drug effects*; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000494:pharmacology
D000975:Antioxidants; D015682:Retroviridae Proteins, Oncogenic; D014810:Vitamin E; D024505:Tocopherols