A
vitamin E derivative,
vitamin E succinate (VES; RRR-alpha-tocopheryl
succinate), and a
vitamin E analogue,
2,5,7,8-tetramethyl-2R-(4R,8R,12-trimethyltridecyl)chroman-6-yloxy acetic acid (alpha-
TEA), induce human breast, prostate, colon, lung, cervical, and endometrial
tumor cells in culture to undergo apoptosis but not normal human mammary epithelial cells, immortalized, nontumorigenic breast cells, or normal human prostate epithelial cells. Human ovarian and
cervical cancer cell lines are exceptions, with alpha-
TEA exhibiting greater proapoptotic effects. Although both VES and alpha-
TEA can induce A2780 and subline A2780/cp70
ovarian cancer cells to undergo
DNA synthesis arrest within 24 h of treatment, only alpha-
TEA is an effective inducer of apoptosis. VES or alpha-
TEA treatment of cp70 cells with 5, 10, or 20 microg/ml for 3 days induced 5, 6, and 19% versus 9, 36, and 71% apoptosis, respectively. Colony formation data provide additional evidence that cp70 cells are more sensitive to growth inhibition by alpha-
TEA than VES. Differences in stability of the
ester-linked
succinate moiety of VES versus the
ether-linked
acetic acid moiety of alpha-
TEA were demonstrated by high-performance liquid chromatography analyses that showed alpha-
TEA to remain intact, whereas VES was hydrolyzed to the free
phenol, RRR-
alpha-tocopherol. Pretreatment of cp70 cells with
bis-(p-nitrophenyl) phosphate, an
esterase inhibitor, before VES treatment, resulted in increased levels of intact VES and apoptosis. Taken together, these data show alpha-
TEA to be a potent and stable proapoptotic agent for human ovarian
tumor cells and suggest that endogenous ovarian
esterases can hydrolyze the
succinate moiety of VES, yielding RRR-
alpha-tocopherol, an ineffective apoptotic-inducing agent.