Abstract 5237: Protection of tocopherols against estrogen-induced breast cancer via mechanisms targeting cancer stem cells

Estrogens have been implicated to be complete carcinogens through mechanisms involving increased proliferation, oxidative stress and DNA damage. Although the importance of estrogen in breast cancer is well established, the effects of estrogen on breast cancer stem cells are not fully understood. Due to the role of breast cancer stem cells in tumor initiation, maintenance, and progression, targeting cancer stem cells has become important for understanding estrogen-mediated breast carcinogenesis. The vitamin E family, which is consisted of four different forms of tocopherols and tocotrienols, has been shown to exert anti-tumor effects in animal models of various cancers. In the present study, we examined the protective effects of α-, γ-, δ-tocopherol as well as a natural γ-tocopherol rich mixture of tocopherols (γ-TmT) against estrogen-induced expansion of cancer stem-like cells and estrogen-mediated tumor growth. To determine the effects of tocopherols on breast cancer stem cells, the MCF-7 mammosphere cell culture system, which enriches for mammary progenitor cells and putative breast cancer stem cells, was utilized. Treatment of MCF-7 mammosphere with estrogen for six days resulted in an increase in CD44+/CD24- stem-like cell populations as well as the number and size of mammosphere. α-, γ-, δ-Tocopherol, and most significantly γ-TmT, inhibited estrogen-induced mammosphere formation, indicating that tocopherols reverse estrogen-induced expansion of breast cancer stem cells. In MCF-7 xenograft tumor study, MCF-7 cells (5 × 106 cells/mouse) were injected into the mammary fat pad in immunodeficient mice after subcutaneous implantation with 0.72 mg of estrogen pellet. Mice were then administered with diets containing 0.2% α-, γ-, δ-tocopherol and γ-TmT for 5 weeks. Treatment of α-, γ-, δ-tocopherol or γ-TmT reduced the tumor volume by 71% (p Citation Format: Min Ji Bak, Soumyasri Das Gupta, Joseph Wahler, Mao-Jung Lee, Yong Lin, Weichung Joe Shih, Chung S Yang, Nanjoo Suh. Protection of tocopherols against estrogen-induced breast cancer via mechanisms targeting cancer stem cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5237.