BET inhibitor JQ1 induces apoptosis of ovarian and endometrial endometrioid carcinoma cells by downregulating <i>c‑Myc</i>
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 <i>c-Myc</i> 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.
Authors
- Futaba Inoue
- Katsutoshi Oda (ORCID: https://orcid.org/0000-0002-2468-9573)
- Tomohiko Fukuda (ORCID: https://orcid.org/0000-0003-2711-3067)
- Ryuji Hamamoto (ORCID: https://orcid.org/0000-0002-2632-1334)
- Yasushi Hirota (ORCID: https://orcid.org/0000-0003-0241-9780)
- Yutaka Osuga (ORCID: https://orcid.org/0000-0002-6660-1066)
- Ayumi Taguchi (ORCID: https://orcid.org/0000-0002-5491-3871)
- Natsumi Tsuboyama (ORCID: https://orcid.org/0000-0002-8620-3479)
- Eri Suzuki
- Osamu Wada‐Hiraike (ORCID: https://orcid.org/0000-0002-3458-6711)
- Yusuke Toyohara (ORCID: https://orcid.org/0000-0001-9417-7496)
- Syuzo Kaneko (ORCID: https://orcid.org/0000-0003-4558-9800)
- Ken Asada (ORCID: https://orcid.org/0000-0003-0548-4449)
- Saki Tanimoto
- Mayuyo Mori
- Takayuki Iriyama (ORCID: https://orcid.org/0000-0001-7970-6695)
- Kenbun Sone (ORCID: https://orcid.org/0000-0002-7218-6401)
- Ryuta Hachijo
- Yuichiro Miyamoto
- Masaaki Komatsu (ORCID: https://orcid.org/0000-0003-0421-8085)
- Harunori Honjoh (ORCID: https://orcid.org/0009-0004-3953-6010)
- Yuri Jonouchi
Institutions
- The University of Tokyo (JP)
Publication Details
- Journal
- Oncology Letters
- Published
- 2024-12-19
- DOI
- https://doi.org/10.3892/ol.2024.14852
- Citations
- 2
- Primary Topic
- Protein Degradation and Inhibitors
- Type
- article
- Field-Weighted Citation Impact
- 0.47
Funders
- Ministry of Education, Culture, Sports, Science and Technology