RRR-α-tocopheryl succinate inhibits human gastric cancer SGC-7901 cell growth by inducing apoptosis and DNA synthesis arrest

摘要

AIM: To investigate the effects of growth inhibition of human gastric cancer SGC-7901 cell with RRR-α-tocopheryl succinate (VES), a derivative of natural Vitamin E, via inducing apoptosis and DNA synthesis arrest.METHODS: Human gastric cancer SGC-7901 cells were regularly incubated in the presence of VES at 5, 10 and 20 mg·L^-1 (VES was dissolved in absolute ethanol and diluted in RPMI 1640 complete condition media correspondingly to a final concentration of VES and 1 mL·L^-1 ethanol), succinic acid and ethanol equivalents as vehicle (VEH) control and condition media only as untreated (UT) control. Trypan blue dye exclusion analysis and MTT assay were applied to detect the cell proliferation. 37 kBq of tritiated thymidine was added to cells and [³H] TdR uptake was measured to observe DNA synthesis. Apoptotic morphology was observed by electron microscopy and DAPI staining. Flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay were performed to detect VES-triggered apoptosis.RESULTS: VES inhibited SGC-7901 cell growth in a dose-dependent manner. The growth curve showed suppression by 24.7%, 49.2% and 68.7% following 24 h of VES treatment at 5, 10 and 20 mg·L^-1, respectively, similar to the findings from MTT assay. DNA synthesis was evidently reduced by 35%, 45% and 98% after 24 h VES treatment at 20 mg·L^-1 and 48 h at 10 and 20 mg·L^-1, respectively. VES induced SGC-7901 cells to undergo apoptosis with typically apoptotic characteristics, including morphological changes of chromatin condensation, chromatin crescent formation/margination, nucleus fragmentation and apoptotic body formation, typical apoptotic sub-G1 peak by flow cytometry and increase of apoptotic cells by TUNEL assay in which 90% of cells underwent apoptosis after 48h of VES treatment at 20 mg·L^-1.CONCLUSION: VES can inhibit human gastric cancer SGC-7901 cell growth by inducing apoptosis and DNA synthesis arrest. Inhibition of SGC-7901 cell growth by VES is dose-and time-dependent. Therefore VES can function as a potent chemotherapeutic agent against human gastric carcinogenesis.