| RRR-α-tocopheryl succinate (vitamin E succinate, VES), a derivative of natural vitamin E, is a potent inhibitor of various cancer cell types in vitro and in vivo. VES is noteworthy not only for its antiproliferative effects on tumor cells but also for its non-toxic effects on normal cells. This paper will focus on VES-induced growth inhibition and apoptosis in human gastric cancer SGC-7901 cells, and on the roles of mitogen-activated protein kinases (MAPKs). It was demonstrated that VES obviously inhibited the growth of SGC-7901 cells and triggered apoptosis with typically morphological and biochemical characteristics. The roles of ERK1/2, JNK and p38 pathways were determined respectively. The results showed that phosphorylation of ERK1/2 was transiently activated, but inhibited after 24h of VES treatment. VES reduced the expression of Elk-1 mRNA. Antisense to Elk-1 oligomers did not alter VES-triggered apoptotic rate. VES not only increased the expression of both phospho-JNK and c-Jun mRNA and protein, but also prolonged their activation. Dominant negative JNK1 significantly reduced the expression of c-Jun protein and VES-mediated apoptosis. Antisense oligomers to c-Jun also decreased VES-induced apoptosis. VES had no effects on p38 and ATF-2. Antisense to ATF-2 oligomers also had no effect on VES-mediated apoptotic rate. The data above support that VES is a potent growth inhibitor of human gastric cancer cells and MAPKs, especially ERK1/2 and JNK, are important components of VES-mediated cell death. It is implicated that VES may act as a potential chemopreventive/chemotherapeutic agent.
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