Abstract 912: Sulforaphane suppresses the growth of triple-negative breast cancer stem-like cells in vitro and in vivo

Abstract

Abstract Approximately 10-20% of breast cancer consists of triple-negative tumors, which present the poorest prognosis among the different subtypes. The triple-negative breast cancer (TNBC) tumors are known to be enriched with stem-like cells that are resistant to standard targeted drugs. Thus, it is extremely important to develop new agents that are non-toxic and specifically efficacious against these cancer stem-like cells (CSCs) that are suggested to be responsible for the initiation and maintenance of tumors. Here, we show that sulforaphane (SFN), a dietary component abundant in broccoli and broccoli sprouts, inhibits cell proliferation and sphere formation of the CSC population in TNBC cells. TNBC stem-like cells were isolated from MDA-MB-231 Luci D3H1human triple negative breast cancer cells using fluorescently activated cell sorting (FACS) analysis. Six week old BalbC/nude mice were purchased from Jackson laboratory and fed with an AIN-96G-purified diet containing no SFN (Harlan Teklad Inc) until the end of experiments. The mice (n = 40) were treated with or without daily i.p. injection of 50mg SFN/kg b.w. for 2 weeks prior to the inoculation with MDA-MB-231 Luci D3H1 cells. The tumor cells were planted into both sides of the 4th inguinal mammary fat pads. The SFN treatment was continued for 3 additional weeks after the tumor cell xenografts. Our results revealed that the CSC population isolated with CD49f+, CD24-/CD44high showed the ability to form mammoshperes, which is a characteristic of stemness. When these cells were treated with natural dietary constituent SFN at the concentration of 7.5 μM, they lost the property of mammosphere formation in vitro. Furthermore, SFN pre-treated animals (n = 20) exhibited a thirty percent reduction in tumor volume compared with control (saline 0.9%) at day 30 after the tumor cell inoculation. These data indicate that SFN suppresses triple negative mammary tumor formation both in vitro (7.5uM) and in vivo (50mg/kg bw) by targeting a CSC population. Further analysis on gene expression and protein profiles are being performed to elucidate whether stem-related developmental signaling pathways are being modulated by SFN. Citation Format: Nadia P. Castro, Cristina M. Rangel, David Salomon, Karen Saylor, Young S. Kim. Sulforaphane suppresses the growth of triple-negative breast cancer stem-like cells in vitro and in vivo. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 912. doi:10.1158/1538-7445.AM2015-912