alpha-Tocopheryl
succinate (TS) is known to induce apoptosis in various cells and has attracted attention as a chemotherapeutic agent. Recently, we reported the structural significance of the terminal dicarboxylic moiety for the action of TS [J. Nutr. Sci. Vitaminol. 49 (2003) 310-314]. In this study, to determine details of the relationship between the structure and the function of the terminal
ester moiety of
alpha-tocopherol (alpha-T), we synthesized four novel
esters,
alpha-tocopheryl oxalate (TO),
alpha-tocopheryl malonate (TM), alpha-tocopheryl pimelate (TP) and alpha-tocopheryl
succinate ethyl
ester (TSE), and compared their apoptogenic activities with those of TS, alpha-T,
gamma-tocopherol (gamma-T) and two commercially available alpha-T derivatives,
alpha-tocopheryl nicotinate (TN) and alpha-
tocopheryl acetate (TA), in vascular smooth muscle cells and a mouse
breast cancer cell line C127I. TO and TM in addition to TS, but not the others, induced apoptosis in both cells. Particularly, TO was the most potent of all alpha-T derivatives used. The addition of exogenous
superoxide dismutase (SOD) significantly prevented the apoptosis induced by TM as well as that by TS as reported previously, but did not affect TO-induced apoptosis. These results suggest that O(2)(-) generated exogenously participates in TM-induced apoptosis but not in TO-induced apoptosis. The difference in their apoptotic effects is attributed to structural properties of the terminal dicarboxylic moiety, which has an inflexible plane conformation in TO, while it is highly flexible in TM and TS.