A phase 2 clinical trial investigating the efficacy and safety of AS602801, a newly developed JNK inhibitor, in the treatment of inflammatory endometriosis is complete. We are now examining whether AS602801 acts against human cancer cells in vitro and in vivo. In vitro, AS602801 exhibited cytotoxicity against both serum-cultured non-stem cancer cells and cancer stem cells derived from human pancreatic cancer, non-small cell lung cancer, ovarian cancer and glioblastoma at concentrations that did not decrease the viability of normal human fibroblasts. AS602801 also inhibited the self-renewal and tumor-initiating capacity of cancer stem cells surviving AS602801 treatment. Cancer stem cells in established xenograft tumors were reduced by systemic administration of AS602801 at a dose and schedule that did not adversely affect the health of the tumor-bearing mice. These findings suggest AS602801 is a promising anti-cancer stem cell agent, and further investigation of the utility of AS602801 in the treatment of cancer seems warranted.

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.

Repurposing aripiprazole as an anticancer stem cell drug may merit further consideration.

GSKJ4, being a promising anticancer agent for NSCLC, may be effective against a wider spectrum of cancers than previously thought.

Glioblastoma multiforme is the most malignant primary intrinsic brain tumor. Glioma stem cells ( GSC s) are associated with chemoradiotherapy resistance and the recurrence of glioblastomas after conventional therapy. The targeting of GSC s is potentially an effective treatment for the long‐term survival of glioblastoma patients. Licochalcone A, a natural chalconoid from licorice root, exerts anticancer effects; however, its effect on GSC s remains unknown. We found that Licochalcone A induced massive caspase‐dependent death in GSC s but not in differentiated GSC s nor normal somatic and neural stem cells. Prior to cell death, Licochalcone A caused mitochondrial fragmentation and reduced the membrane potential and ATP production in GSC s. Thus, Licochalcone A induces mitochondrial dysfunction and shows promise as an anticancer stem cell drug.