Abstract 196: Targeting breast cancer stem cells with a panel of potential ALDH1A3 inhibitors

Abstract

Abstract Aldehyde dehydrogenase (ALDH) isoform ALDH1A3 is selectively expressed in breast cancer stem cells (CSCs) and is a key mediator in breast cancer progression via initiation of retinoic acid (RA) signaling and expression of RA-inducible genes. Expression of ALDH1A3 and its induced RA-inducible genes are associated with less favorable patient outcomes. This suggests that ALDH1A3 represents a novel anti-breast cancer therapeutic target. To target the specific ALDH1A3 isoform, a panel of general ALDH inhibitors was attained and the compounds’ effectiveness in targeting ALDH1A3 activity was quantified by their ability to decrease expression of the downstream genes retinoic acid receptor beta (RARβ) and retinoic acid receptor responder protein 1 (RARRES1). Eleven compounds were tested in total, and the essential oil citral was shown to significantly decrease ALDH1A3-mediated expression of both RA-inducible genes in a dose dependent manner. Citral is already used in cosmetics and food additives and recent work shows that it can induce apoptosis of breast cancer cells making it a promising therapeutic agent and a potential subject of a future xenograft study in mice to determine its effects on CSCs in vivo. Citation Format: Margaret L. Thomas, Melissa Wallace, Carman Giacomantonio, Paola Marcato. Targeting breast cancer stem cells with a panel of potential ALDH1A3 inhibitors. [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 196. doi:10.1158/1538-7445.AM2014-196