BET inhibitor JQ1 induces apoptosis of ovarian and endometrial endometrioid carcinoma cells by downregulating c‑Myc

Oncol Lett. 2024 Dec 19;29(3):106. doi: 10.3892/ol.2024.14852. eCollection 2025 Mar.

Abstract

Although ovarian endometrioid carcinoma (OEC), frequently associated with endometrial endometrioid carcinoma (EEC), is often diagnosed at an early stage, the prognosis remains poor. The development of new, effective drugs to target these cancers is highly desirable. The bromodomain and extra-terminal domain (BET) family proteins serve a role in regulating transcription by recognizing histone acetylation, which is implicated in several types of cancer. BET inhibitors have been reported as promising cancer drugs. The present study aimed to assess the role of JQ1, a BET inhibitor, in ovarian and endometrial cancers. The sensitivity of OEC and EEC cell lines to JQ1 was assessed using cell viability and colony formation assays. Additionally, western blotting and cell cycle assays were performed to evaluate changes in c-Myc expression and apoptosis markers. Cell proliferation and colony formation assays revealed significant tumor suppression in both OEC and EEC cell lines in response to JQ1 treatment. Furthermore, treatment with JQ1 induced a decrease in c-Myc expression and an increase in apoptosis markers, such as cleaved PARP and the cell population in the sub-G1 phase, in both OEC and EEC cell lines. The findings of the present study indicate that JQ1 may induce cell death through c-Myc inhibition and could be a potentially novel therapeutic agent in the treatment in OEC and EEC. However, the direct mechanism, has not been fully elucidated, warranting further investigation.

Keywords: apoptosis; bromodomain and extra-terminal domain protein; c-Myc; endometrioid endometrial carcinoma; epigenetics; ovarian endometrioid carcinoma.

Grants and funding

The present work was supported by a Grant-in-Aid for Scientific Research (B) from the Ministry of Education, Culture, Sports, Science and Technology of Japan (grant no. 20H03820). The present study was also partially supported by BRIDGE programs for Bridging the gap between R&d and the IDeal society (society 5.0) and Generating Economic and social value (grant no. J0125252401h0001).