The ability of the
vitamin E (RRR-
alpha-tocopherol) derivatives alpha-tocopheryl
succinate (alpha-TOS) and
alpha-tocopheryloxyacetic acid (alpha-
TEA) to suppress
tumor growth in preclinical animal models has recently led to increased interest in their potential use for treating human
cancer. To make the use of these
vitamin E analogues more clinically relevant, we compared the antitumor efficacy of orally and i.p. delivered forms of alpha-
TEA and alpha-TOS against a murine
mammary cancer (4T1) that bears resemblance to human
breast cancer because of its poor immunogenicity and high metastatic potential. In cell culture studies, we showed that both compounds inhibited
tumor colony formation and induced apoptotic death of
tumor cells. To avoid solubility concerns associated with the hydrophobicity of alpha-
TEA and alpha-TOS, we used the vesiculated forms of alpha-
TEA (V alpha-
TEA) and alpha-TOS (V alpha-TOS) for the in vivo
tumor studies. Both compounds inhibited the growth of preestablished 4T1
tumors when given i.p. However, when given by oral gavage, only the
esterase-resistant V alpha-
TEA was able to suppress primary
tumor growth and reduce lung
metastasis. To make this approach more translatable to the clinic, alpha-
TEA was incorporated into the diet and fed to
tumor-bearing mice. We report here for the first time that dietary alpha-
TEA delivery significantly inhibited primary
tumor growth and dramatically reduced spontaneous metastatic spread to the lung in prophylactic and therapeutic settings. This study suggests that dietary alpha-
TEA could prove useful as a relatively easy and effective modality for treating metastatic
breast cancer.