Abstract 208: Metformin represses stem cell properties and induces apoptosis in human breast cancer cells and mouse mammary epithelial cells

Abstract

Abstract Cancer stem cells (CSCs) are small portions of cancer cells that have important self-renewal and proliferation characteristics, and therefore, they play a significant role in cancer development and metastasis. Recently, several studies have revealed CSCs of several solid tumors. The identification and targeting of CSCs are expected to advance treatment outcomes, but until now, only a few drugs that specifically target CSCs have been developed. Metformin, an antidiabetic drug used for the treatment of type 2 diabetes mellitus, suppresses gluconeogenesis in the liver and increases insulin sensitivity and glucose uptake in peripheral tissues such as muscles. Moreover, the drug has shown an anti-cancer effect by inhibiting cellular proliferation and protein synthesis in several cancer cell lines. Additionally, many clinical and epidemiological studies have suggested that metformin might be associated with a decreased risk of cancer development and an increased response to chemotherapy. In addition to its anticarcinogenic effect, studies about the anti-cancer stem cell effect of metformin have been recently reported. Several reports revealed that metformin could preferentially kill cancer stem cells, including breast cancer stem cells. However, the mechanism of anti-cancer stem cell activity is not well known. Therefore, this study was planned to confirm the cytotoxicity of metformin, especially for breast cancer stem cells as well as breast cancer cells. To this end, several human breast cancer cell lines and normal mouse mammary epithelial cell lines were used. In this study, metformin showed cell growth inhibition in human breast cancer cells and mouse mammary epithelial cells by inducing cell cycle arrest and apoptosis. Moreover, metformin specifically killed breast cancer stem cells. Metformin showed reduced mammosphere formation in all cell lines. In addition, decreasing breast cancer stem cell population by metformin treatment was identified through FACS analysis. For the mechanism of anti-cancer stem cell activity, western blot assay was performed. We identified decreased levels of cyclin D and cycline E and increased levels of Bax in secondary mammaospheres according to metformin treatment. In conclusion, this present study show that metformin kills breast cancer stem cells as well as breast cancer cells, and these phenomena occur by the induction of cell cycle arrest and apoptosis. Citation Format: Eun Joo Kang, Jae Hong Seo, Jun Suk Kim, Ji Young Kim. Metformin represses stem cell properties and induces apoptosis in human breast cancer cells and mouse mammary epithelial cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 208. doi:10.1158/1538-7445.AM2014-208