Abstract 5261: Tocopherols inhibit the estrogen-stimulated expansion of cancer stem cells via down-regulation of OCT4 and NFκB

Abstract

Abstract Cancer stem cells have been suggested to play a role in tumor initiation, maintenance, resistance, and metastasis. Breast cancer stem cells are defined as CD44+/CD24- cell populations that have the properties of tumor-initiating ability, self-renewal and differentiation. Although the importance of estrogen in breast cancer is well established, the effects of estrogen on breast cancer stem cells are not fully understood. Vitamin E, which is consisted of different forms of tocopherols and tocotrienols, has anti-tumor effects in various cancers, including breast cancer. In the present study, we examined the effects of α-, γ-, and δ-tocopherol against estrogen-stimulated expansion of cancer stem cells. To determine the effects of tocopherols on breast cancer stem cells, the MCF-7 tumorsphere cell culture system, which enriches for mammary progenitor cells and putative breast cancer stem cells, was utilized. Treatment of MCF-7 tumorsphere with estrogen for four days resulted in an increase in CD44+/CD24- stem cell populations in tumorspheres as well as the number and size of tumorspheres. Tocopherols at 1 and 10 μM inhibited formation of estrogen-induced stem cell enriched tumorspheres, indicating that tocopherols reversed estrogen-induced expansion of breast cancer stem cells. Tocopherols decreased the expression of estrogen-related genes such as TFF/pS2, cathepsin D, progesterone receptor and SerpinA1 in estrogen-stimulated tumorspheres. In addition, the mRNA levels of stem cell markers, including OCT4, NFκB, SOX-2 and CD44, were upregulated by estrogen, which were downregulated by the treatment with tocopherols. Our results suggest that tocopherols repress the expansion of breast cancer stem cell population by regulating OCT4 and NFκB signaling. Tocopherols could be effective natural agents for the prevention and treatment of estrogen-induced breast cancer. (This work was supported in part by the National Institutes of Health grant R01 AT007036.) Citation Format: Min Ji Bak. Tocopherols inhibit the estrogen-stimulated expansion of cancer stem cells via down-regulation of OCT4 and NFκB [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5261. doi:10.1158/1538-7445.AM2017-5261