Vitamin E analogues as inducers of apoptosis: implications for their potential antineoplastic role.
Recent evidence suggests that vitamin E and its analogues, which have been used for many years as antioxidants, may not only protect cells from free radical damage but also induce apoptotic cell death in various cell types. While alpha-tocopherol (alpha-TOH) is mainly known as an anti-apoptotic agent, its redox-silent analogues either have no influence on cell survival (alpha-tocopheryl acetate, alpha-TOA), or induce apoptosis (alpha-tocopheryl succinate, alpha-TOS). Although precise mechanisms of apoptosis induction by alpha-TOS remain to be elucidated, there is evidence that this process involves both the antiproliferative and membrane destabilising activities of the agent. Alpha-TOS has been shown to induce apoptosis in malignant cell lines but not, in general, in normal cells, and to inhibit tumorigenesis in vivo. These features suggest that this semi-synthetic analogue of vitamin E could be a promising antineoplastic agent.
Neuzil
J
J
Institute for Prevention of Cardiovascular Diseases, Ludwig Maximilians University, Munich, Germany. jneuzil@klp.med.uni-muenchen.de
Weber
T
T
Terman
A
A
Weber
C
C
Brunk
U T
UT
D000230:Adenocarcinoma / Q000188:drug therapy; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy; D004354:Drug Screening Assays, Antitumor; D016166:Free Radical Scavengers / Q000494:pharmacology / Q000627:therapeutic use; D005609:Free Radicals; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects; D007425:Intracellular Membranes / Q000187:drug effects; D008247:Lysosomes / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D008819:Mice, Nude; D008928:Mitochondria / Q000187:drug effects; D015394:Molecular Structure; D014411:Neoplastic Stem Cells / Q000187:drug effects; D010084:Oxidation-Reduction; D011493:Protein Kinase C / Q000502:physiology; D017382:Reactive Oxygen Species; D015398:Signal Transduction / Q000187:drug effects; D013234:Stem Cells / Q000187:drug effects; D024505:Tocopherols; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D000975:Antioxidants; D016166:Free Radical Scavengers; D005609:Free Radicals; D017382:Reactive Oxygen Species; D014810:Vitamin E; D011493:Protein Kinase C; D024505:Tocopherols