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Dietary administration of the proapoptotic vitamin E analogue alpha-tocopheryloxyacetic acid inhibits metastatic murine breast cancer.
Cancer Res. 2006 Oct 01; 66(19):9374-8.CR

Abstract

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.

Authors+Show Affiliations

Department of Immunobiology, Arizona Cancer Center, BIO5 Institute for Collaborative Bioresearch, University of Arizona, Tucson, AZ 85724, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

17018590

Citation

Hahn, Tobias, et al. "Dietary Administration of the Proapoptotic Vitamin E Analogue Alpha-tocopheryloxyacetic Acid Inhibits Metastatic Murine Breast Cancer." Cancer Research, vol. 66, no. 19, 2006, pp. 9374-8.
Hahn T, Szabo L, Gold M, et al. Dietary administration of the proapoptotic vitamin E analogue alpha-tocopheryloxyacetic acid inhibits metastatic murine breast cancer. Cancer Res. 2006;66(19):9374-8.
Hahn, T., Szabo, L., Gold, M., Ramanathapuram, L., Hurley, L. H., & Akporiaye, E. T. (2006). Dietary administration of the proapoptotic vitamin E analogue alpha-tocopheryloxyacetic acid inhibits metastatic murine breast cancer. Cancer Research, 66(19), 9374-8.
Hahn T, et al. Dietary Administration of the Proapoptotic Vitamin E Analogue Alpha-tocopheryloxyacetic Acid Inhibits Metastatic Murine Breast Cancer. Cancer Res. 2006 Oct 1;66(19):9374-8. PubMed PMID: 17018590.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dietary administration of the proapoptotic vitamin E analogue alpha-tocopheryloxyacetic acid inhibits metastatic murine breast cancer. AU - Hahn,Tobias, AU - Szabo,Lajos, AU - Gold,Mikhal, AU - Ramanathapuram,Lalitha, AU - Hurley,Laurence H, AU - Akporiaye,Emmanuel T, PY - 2006/10/5/pubmed PY - 2007/11/7/medline PY - 2006/10/5/entrez SP - 9374 EP - 8 JF - Cancer research JO - Cancer Res VL - 66 IS - 19 N2 - 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. SN - 1538-7445 UR - https://www.unboundmedicine.com/medline/citation/17018590/Dietary_administration_of_the_proapoptotic_vitamin_E_analogue_alpha_tocopheryloxyacetic_acid_inhibits_metastatic_murine_breast_cancer_ L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=17018590 DB - PRIME DP - Unbound Medicine ER -