Abstract 961: Higher activity of δ-tocopherol (δ-T) than γ-tocopherol and α-tocopherol in the inhibition of lung cancer H1299 xenograft tumors in mice

Our previous study showed that γ-TmT (a tocopherol mixture containing 57% γ-T, 24% δ-T, 13% α-T and 1.5% β-T) effectively inhibited colon and lung carcinogenesis as well as the growth of transplanted human lung cancer in mice. This study aims to determine the more active constituents in this mixture in a xenograft model. After injection of human lung cancer H1299 cells into NCr nu/nu nude mice, the mice were maintained on a standard AIN93M diet or diet enriched with α-T, γ-T, δ-T or γ-TmT (each at 0.3% and 0.17%) for 50 days. Dietary δ-T showed the strongest inhibition based on final tumor weight (35.6% and 57.6% reduction from the control by 0.17% and 0.3% δ-T, respectively). Dietary 0.3% γ-T and γ-TmT also showed significant inhibition (37.4% and 46% reduction from control, respectively). However, an inhibitory effect was not observed with dietary α-T group. Consistent with the animal study, the growth of H1299 cells was inhibited by tocopherols with their effectiveness following the order of δ-T > γ-TmT > γ-T, but α-T was not effective. We also found that dietary α-T, γ-T and δ-T treatment respectively increased serum α-T, γ-T and δ-T levels (up to 45, 9.7 and 1.2μM, respectively). However, the serum α-T level was decreased by dietary γ-T and δ-T; for example, at 0.3% they decreased α-T levels by 50% and 42% from the control group, respectively. The results suggest a competition among different forms of tocopherols. Dietary treatment with each form of tocopherol also increased the corresponding side-chain degradation metabolites: carboxyethyl hydroxychromans (CEHC) and carboxymethylbutyl hydroxychromans (CMBHC). With 0.3% α-, γ- and δ-T in the diet, the mean serum levels of α-, γ- and δ-CEHC were 0.08, 0.7 and 3.0μM, respectively; and α-, γ- and δ-CMBHC were 0.14, 0.83 and 4.0μM, respectively. These metabolites retain the intact chromanol ring and, similar to their parent tocopherols, could trap reactive oxygen and nitrogen species. δ-CEHC and δ-CMBHC, which are present at rather high concentrations, may play an important role in inhibiting xenograph and tumor growth. The present results show that δ-T and γ-T effectively inhibited human lung cancer xenograft tumors and the inhibition may be due to the apoptosis-inducing, antioxidative, and reactive nitrogen species-trapping activities of these tocopherols and their metabolites (Supported by NIH grants CA120915, CA122474, and CA133021). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 961.