Abstract 3834: Epigenetic modification of oncogenes or tumor suppressor genes by thymoquinone in triple negative breast cancer

Abstract

Abstract Background and Objective: Triple negative breast cancer (TNBC) is a molecular subtype, and most aggressive and deadly among breast cancers. Different molecular subtypes of breast cancer have distinct molecular mechanisms, and in case of TNBC, the mechanisms are complex, and still obscure. Development of therapeutic strategies are thus also difficult against TNBC. Thymoquinone (TQ) is a natural compound, which has been found effective against TNBC cells, but the mechanism of TQ action in TNBC is not clear. In this study, we have focused on TQ’s genome-wide epigenetic effect on TNBC cell line BT549. Methods: The BT549 cells were treated with 1-10 µM of TQ for cellular growth analysis, and isolated DNA for dot blot analysis with anti-5-methyl cytosine (anti-5MC) antibody to observe whole genome methylation status affected by TQ. Also the chromatin immunoprecipitation (ChIP) was performed with anti-methyl binding domain protein (anti-MBD1) to identify DNA sections, of which methylation status is changed by TQ. Results: Cell viability assay showed that TQ dose-dependently reduced BT549 cell growth. DNA dot blot analysis results indicated no obvious changes in total methylation status change in genomic DNA. However, ChIP-seq confirmed that methylation level was affected (either increased or decreased) in certain genomic locations by TQ treatment. Some of the locations are proximal or close to some genes, indicating that this epigenetic modification might have influence on these genes’ expression pattern. Conclusion: Thus, here in this preliminary research study, we indicate some genes, which might be epigenetically targeted by TQ in TNBC cells. Funding support: National Natural Science Foundation of China (Grant No. 81850410555, 81672887, 81172049) Citation Format: Md. Asaduzzaman Khan, Meiling Zheng, Junjiang Fu. Epigenetic modification of oncogenes or tumor suppressor genes by thymoquinone in triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3834.