Background/Aim: Global increase in the trimethylation of histone H3 at lysine 27 (H3K27me3) has been associated with the differentiation of normal stem cells and cancer cells, however, the role of H3K27me3 in the control of cancer stem cells (CSCs) remains poorly understood. We investigated the impact of increased H3K27me3 on ovarian CSCs using GSKJ4, a selective jumonji H3K27 demethylase inhibitor.

Materials and Methods: The effect of GSKJ4 on the viability as well as on the self-renewal and tumor-initiating capacity of CSCs derived from A2780 and TOV21G human ovarian cancer cell line, was examined.

Results: GSKJ4 induced cell death in A2780 CSC and TOV21G CSC at a concentration non-toxic to normal human fibroblasts. Furthermore, GSKJ4 induced differentiation and inhibited sphere formation as well as stem cell marker expression of A2780 CSC and TOV21G CSC that survived GSKJ4 treatment.

Conclusion: Using ovarian CSCs as a model, we have demonstrated for the first time that GSKJ4 can target CSCs, suggesting a critical role for H3K27 methylation in their maintenance and survival. Our findings thus provide an initial clue to explore the role of GSKJ4 as a potent CSC-targeting agent for ovarian cancer and other types of human cancer.

Citation Format: Hirotsugu Sakaki. GSKJ4, a selective jumonji histone H3 lysine27 demethylase inhibitor, targets ovarian cancer stem cells [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 158.