Abstract 5949: Artesunate influences the transcripts for Eph receptors and ephrin ligands in breast cancer cells

Abstract

Abstract Purpose: Artesunate (ART), an anti-malarial drug, has been shown to induce apoptosis in breast cancer cells. The current study was conducted to explore the involvement of Eph receptor and ephrin ligand transcript levels in mediating apoptotic functions of ART in three phenotypically distinct breast cell lines. The specific involvement Eph receptors and ephrin ligands in apoptosis may potentially lead to novel approaches for therapeutic intervention of breast cancer. Methods: We cultured three cell lines that represent non-tumorigenic breast epithelium (MCF10A), non-invasive breast carcinoma (MCF7), and invasive triple negative breast carcinoma (MDA- MB-231) in the presence of varying concentrations of ART. Total RNA was isolated from untreated and ART-treated cell lines, and the relative abundance of Eph receptor and ephrin ligand transcripts was determined by qPCR. The changes in selected transcripts were confirmed by immunocytochemistry and western blot analysis. Results: Our study revealed that the transcripts corresponding to various Eph receptors and ephrin ligands are differentially expressed in a cell line specific manner in ART-treated cells. Specifically, EphA5 was upregulated and EphB4 was significantly downregulated in MCF10A cells. However, MDA-MB-231 cells were distinguished by upregulation of ephrinA2 and downregulation of EphA7, respectively. MCF7 also showed distinct response to ART treatment. Combinatorial alterations in transcript abundance for a subset of Eph receptors and ephrin ligands are likely to provide meaningful insights in the apoptotic effects of ART in breast cancer cells. Conclusions: A variety of experiments directly or indirectly support the role of Eph receptors and ephrin ligands in apoptosis of numerous cell types. To our knowledge, there have been no conclusive studies to implicate these molecules in ART-mediated cell death. We have demonstrated cell line-specific alterations in the levels of Eph/ephrin transcripts in cells primed for apoptosis by ART-treatment. Specifically, EphA5, EphA7, EphB4 and ephrin A2 appear to transduce apoptotic signals in ART-treated cells. These observations set the basis for pursuing additional mechanistic investigations to decipher novel mediators of apoptosis in breast cancer cells. Citation Format: Tanin Zadeh, Mariana Lucero, Raj Kandpal. Artesunate influences the transcripts for Eph receptors and ephrin ligands in breast cancer cells [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5949.