Bractoppin, a BRCA1 carboxy-terminal domain (BRCT) inhibitor, suppresses tumor progression in ovarian borderline tumor organoids.

Yicong Wan, Yashuang Zhang, Huangyang Meng, Huixian Miao, Yi Jiang, Lin Zhang, Wenjun Cheng

Biochemical and biophysical research communications 2023 Jan 01

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Borderline ovarian tumors are a special class of ovarian tumors between benign and malignant, which are not sensitive to traditional chemotherapy regimens, and the development of target drugs is limited due to the lack of cell lines. Tumor organoids can well preserve the genetic characteristics of the primary tumor, but there are only a few reports of application in borderline tumors. In this study, we successfully generated 13 ovarian borderline tumor organoids and tested the antitumor activity of Bractoppin, a BRCA1 carboxy-terminal domain (BRCT) inhibitor. Bractoppin promotes organoid apoptosis. Mechanistically, Bractoppin can inhibit organoid cell cycle progression, inhibit the repair of DSB damage and promote tumor cell apoptosis. In addition, Bractoppin can also promote the apoptosis of ovarian cancer cell lines and inhibit the HR and NHEJ repair ability of tumor cells. We demonstrate the value of ovarian borderline tumor organoids in the exploration of molecular therapy drugs, and Bractoppin may be a valuable small molecule drug in the treatment of BOT. Copyright © 2022 Elsevier Inc. All rights reserved.

Citation

Yicong Wan, Yashuang Zhang, Huangyang Meng, Huixian Miao, Yi Jiang, Lin Zhang, Wenjun Cheng. Bractoppin, a BRCA1 carboxy-terminal domain (BRCT) inhibitor, suppresses tumor progression in ovarian borderline tumor organoids. Biochemical and biophysical research communications. 2023 Jan 01;638:76-83