RRR-alpha-tocopheryl succinate inhibits human gastric cancer SGC-7901 cell growth by inducing apoptosis and DNA synthesis arrest.
OBJECTIVE
To investigate the effects of growth inhibition of human gastric cancer SGC-7901 cell with RRR-alpha-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 20mg x 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 x 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. Cells were pulsed with 37kBq of tritiated thymidine 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 24h of VES treatment at 5, 10 and 20 mg x L(-1), respectively, similar to the findings from MTT assay. DNA synthesis was evidently reduced by 35%, 45% and 98% after 24h VES treatment at 20mg x L(-1) and 48 h at 10 and 20mg x 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 48 h of VES treatment at 20 mg x L(-1).


CONCLUSIONS
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.
Wu
Kun
K
Department of Nutrition and Food Hygiene, Public Health School, Harbin Medical University, Harbin 150001, Heilongjiang Province,China. wukun@public.hr.hl.cn
Zhao
Yan
Y
Liu
Bai-He
BH
Li
Yao
Y
Liu
Fang
F
Guo
Jian
J
Yu
Wei-Ping
WP
D017209:Apoptosis / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D020287:In Situ Nick-End Labeling; D013274:Stomach Neoplasms; D024505:Tocopherols; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000494:pharmacology*
D014810:Vitamin E; D004247:DNA; D024505:Tocopherols