Synthesis Of α-Tocopheryl Succinate And The Study Of Its Antineoplastic Effect

α-Tocopheryl succinate(α-TOS) is a derivative of α-tocopherol(α-TOH), the main component of natural vitamin E. Recent studies have discovered that α-TOS, excepted acting as a proffer of vitamin E, is an antineoplastic agent. The antineoplastic properties of α-TOS appear to be unique to α-TOH and other derivatives. α-TOS is noteworthy not only for its high selectivity for malignant cells but also for being non-toxic to normal cells. In this study, we first synthesized α-TOS, then its acute, hereditary toxicity and mutagenicity were tested, the effects of α-TOS on the inhibiton of proliferation and induction of apoptosis of human gastric SGC-7901 cells were examined and the function form was explored. Besides, the mice loaded with S180 sarcoma and Ehrlich ascitesocarcinoma was applied for tumor models, the inhibiting effects on the growth of tumor and the mechanism ofα-TOS were investigated. The main results are summarized as follows: 1. α-TOS was synthesized by reacting α-TOH with succinate anhydrite in the presence of catalyst and its structure has been confirmed it by HPLC, IR, MS, 1H-NMR, 13C-NMR. 2. The acute test results showed that the LD50 of α-TOS in mice and rats were 1000mg/kg·bw and over. Referring to the acute toxicity standard rules, it has low toxicity and the negative results of the micronucleus test of bone marrow cell, the sperm shape abnormality test in mice and the ames test proved that α-TOS does not have hereditary toxicity and mutagenicity. 3. The proliferation of SGC-7901 cells was inhibited by α-TOS, the proapoptotic action of α-TOS at concentration 10μg/ml and 20μg/ml were confirmed by morphological , by biochemical characteristics and by flow cytometry. The intract form of α-TOS which induces the apoptosis of SGC-7901 cells was demonstrated by HPLC.