Abstract 5500: Nitric oxide donor DETA/NO inhibits the growth of endometrial cancer cells by upregulating expression of RASSF1 and CDKN1

Abstract

Abstract Nitric oxide (NO), a small signaling molecule, is implicated in several biological processes including cancer progression. At low concentrations, it promotes cell survival and tumor progression, and at high concentrations it causes apoptosis and cell death. To date, the effects of NO donor on human endometrial cancer are largely unknown. Four endometrial cancer cell lines (Ishikawa, AN3CA, KLE and HEC-1B) with varying degrees of genetic complexity were treated with different concentrations (50-500 μM) of DETA/NO for 24 to 120 h. The effects of treatment on cell viability and invasion was determined using MTS, and Boyden chamber assays respectively. Treatment of endometrial cancer cells with DETA/NO induced a dose and time-dependent decrease in cell viability. Ishikawa and AN3CA cells were more responsive to DETA/NO induced growth inhibition compared to HEC-1B and KLE cells. Furthermore, DETA/NO effectively inhibited invasive potential of endometrial cancer cells. To understand the mechanisms by which DETA/NO elicits anti-cancer effects, RNA sequencing (RNA-seq) was used to ascertain alterations in the transcriptomes of human endometrial cancer cells. AN3CA, KLE, Ishikawa, and HEC-1B were treated with DETA/NO for 24 h and RNA was extracted. RNA-seq analysis revealed that of the twenty-one top differentially expressed genes, fourteen were upregulated and seven were downregulated in endometrial cancer cells with DETA/NO. The genes that were upregulated in all four cell lines with DETA/NO were tumor suppressors, RASSF1 and CDKN1A. The expression patterns of these genes were confirmed by Western blotting. Taken together, the results provide the first evidence in support of the anti-cancer effects of DETA/NO in endometrial cancer. Citation Format: Hannah Taitz, Ana Paucarmayta, Robert Cheng, George L. Maxwell, Chad A. Hamilton, David A. Wink, Viqar Syed. Nitric oxide donor DETA/NO inhibits the growth of endometrial cancer cells by upregulating expression of RASSF1 and CDKN1 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5500.