Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jun 8.
doi: 10.1002/1878-0261.70050. Online ahead of print.

The anticancer effect of the HDAC inhibitor belinostat is enhanced by inhibitors of Bcl-xL or Mcl-1 in ovarian cancer

Cécilia Thomine  1 , Sterenn Guillemot  1 , Louis-Bastien Weiswald  1   2   3 , Romane Florent  3 , Edwige Abeilard  1   2 , Florence Giffard  1   2   4 , Emilie Brotin  5 , Mélanie Briand  1   2   6   7 , Enora Dolivet  1   2   8 , Laurent Poulain  1   2   3   6   7 , Marie Villedieu  1
Affiliations
Free article

The anticancer effect of the HDAC inhibitor belinostat is enhanced by inhibitors of Bcl-xL or Mcl-1 in ovarian cancer

Cécilia Thomine et al. Mol Oncol. .
Free article

Abstract

Identifying innovative therapeutic strategies is crucial to improve clinical management of ovarian cancer. Previously, we showed that ovarian cancer cell apoptosis can be triggered by inhibiting the anti-apoptotic proteins Bcl-xL and Mcl-1 and/or by inducing their pro-apoptotic partners Bim, Puma, and Noxa. The expression of these pro-apoptotic proteins can be hindered by excessive histone deacetylation, resulting from HDAC overexpression. This study aimed to evaluate whether belinostat, an FDA-approved pan-HDAC inhibitor, could increase Bim, Puma, and/or Noxa expression and induce ovarian cancer cell death, either alone or in combination with strategies targeting Bcl-xL or Mcl-1. Belinostat exerted a cytostatic effect and, at higher concentrations, an apoptotic effect in SKOV3 and IGROV1-R10 ovarian cancer cells. It induced a concentration-dependent increase in Bim, Puma, and Noxa protein expression, while partially repressing that of Bcl-xL. Inhibition of Bcl-xL sensitized both cell lines to belinostat, as did inhibition of Mcl-1 in IGROV1-R10 cells. Interestingly, belinostat's anticancer activity was also enhanced by inhibitors of Bcl-xL or Mcl-1 in patient-derived tumor organoids. This study therefore positions belinostat-based strategies as promising therapies for ovarian cancer.

Keywords: Bcl‐xL inhibitor; HDAC inhibitor; Mcl‐1 inhibitor; ovarian cancer; targeted therapy.

PubMed Disclaimer

References

    1. Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin. 2023;73(1):17–48.
    1. Lheureux S, Gourley C, Vergote I, Oza AM. Epithelial ovarian cancer. Lancet. 2019;393(10177):1240–1253.
    1. Banerjee S, Moore KN, Colombo N, Scambia G, Kim BG, Oaknin A, et al. Maintenance olaparib for patients with newly diagnosed advanced ovarian cancer and a BRCA mutation (SOLO1/GOG 3004): 5‐year follow‐up of a randomised, double‐blind, placebo‐controlled, phase 3 trial. Lancet Oncol. 2021;22(12):1721–1731.
    1. Correia C, Lee SH, Meng XW, Vincelette ND, Knorr KL, Ding H, et al. Emerging understanding of Bcl‐2 biology: implications for neoplastic progression and treatment. Biochim Biophys Acta. 2015;1853(7):1658–1671. https://doi.org/10.1016/j.bbamcr.2015.03.012
    1. Villedieu M, Louis MH, Dutoit S, Brotin E, Lincet H, Duigou F, et al. Absence of Bcl‐xL down‐regulation in response to cisplatin is associated with chemoresistance in ovarian carcinoma cells. Gynecol Oncol. 2007;105(1):31–44. https://doi.org/10.1016/j.ygyno.2006.12.011

LinkOut - more resources