Prognosis of patients with late stage BCa still remains poor, mostly due to development of chemoradioresistance followed by tumor recurrence. Cancer stem cells (CSCs), with higher drug efflux capability, and other stem cell-like properties were proposed to be responsible for resistance, relapse and progression of BCa. We have shown that EF24 alleviates radiation (IR)-orchestrated NFkB mediated clonal expansion. Herein, we investigated the potential of EF24 in the regulation of IR-induced NFkB dependent stemness in triple negative breast cancer cells (TNBC). MDA-MB-231 cells exposed to mock-IR or IR (2Gy) with/without EF24 were examined for transcriptional alterations of 93 EMT, CSCs self-renewal, pluoripotentcy maintenance and other stem cell markers. NFkB (p50/p65) overexpression (with or without EF24) and RelA siRNA knockout (with IR) approach were used to delineate the role of IR-induced NFkB and the selective NFkB targeting of EF24 in this setting. Nanog, Sox-2, ABCG-2, N-Cadherin, POU5F1 and Myc expression was examined with immunoblotting. IR profoundly increased the transactivation of 86 stem-cell related molecules in TNBCs that are involved in cell survival. Interestingly, muting IR-induced NFkB attenuated 85 of those genes. Notably, EF24 suppressed identical 85 genes reproducing the inhibitory signature of NFkB muting. Coherently, activating NFkB induced 87 stem-cell related molecules in TNBC and of which 86 genes were completely suppressed with EF24. Alterations in the cellular expression levels of Nanog, Sox-2, ABCG-2, N-Cadherin, POU5F1 and Myc validates the potential of EF24 in mitigating IR-induced stemness in TNBC. Together these data demonstrates, at least in TNBC cells, IR-induced NFkB mediates increased stem-like characteristics and further imply that EF24 may alleviate stemness by selectively targeting IR-induced NFkB.

Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-16-02.