A novel stilbene derivative targets RAD51 activity and sensitizes DU145 prostate cancer cells to cisplatin
Abstract
Homologous recombination (HR) is a high-fidelity DNA repair pathway responsible for the resolution of double- strand breaks, with the RAD51 recombinase playing a pivotal role through the formation of nucleoprotein fil- aments on single-stranded DNA. Overexpression of RAD51 is frequently observed in cancer cells, where it pro- motes genome stability under genotoxic stress and contributes to acquired resistance to DNA-damaging chemotherapeutic agents. In this study, we report the identification of a novel stilbene-derived compound, the disodium salt of 4,4′-diphenylcarbamate stilbene-2,2′-disulfonic acid (DPDS), as a novel compound that modu- lates RAD51 monomer–monomer interactions and reduces its binding to single-stranded DNA and ATP, processes that are critical for filament assembly and homologous recombination. Furthermore, DPDS enhances the cyto- toxic effect of cisplatin in DU145 prostate cancer cells and was associated with reduced RAD51 nuclear foci formation and increased accumulation of DNA double-strand breaks. Notably, DPDS did not significantly affect cell viability in the four cellular models evaluated under our experimental conditions and displayed lower intrinsic cytotoxicity than DIDS (4,4′-diisothiocyanostilbene-2,2′-disulfonic acid) and emzadirib. Collectively, these findings support that DPDS as a chemical modulator of RAD51 activity may enhance cisplatin sensitivity in DU145 prostate cancer cells.
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BibTeX
@article{fonteneau2026novel,
title = {{A novel stilbene derivative targets RAD51 activity and sensitizes DU145 prostate cancer cells to cisplatin}},
author = {Lucie Fonteneau and Houda Benhelli-Mokrani and Céline Robiou Du Pont and Damien Marquis and Jacques Lebreton and Monique Mathé-Allainmat and Benoît Chénais and Fabrice Fleury},
journal = {Biochemical Pharmacology},
year = {2026},
month = aug,
doi = {10.1016/j.bcp.2026.118393},
url = {https://hal.science/hal-05761193v1},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - A novel stilbene derivative targets RAD51 activity and sensitizes DU145 prostate cancer cells to cisplatin
AU - Lucie Fonteneau
AU - Houda Benhelli-Mokrani
AU - Céline Robiou Du Pont
AU - Damien Marquis
AU - Jacques Lebreton
AU - Monique Mathé-Allainmat
AU - Benoît Chénais
AU - Fabrice Fleury
PY - 2026
DA - 2026/08/24
JO - Biochemical Pharmacology
DO - 10.1016/j.bcp.2026.118393
UR - https://hal.science/hal-05761193v1
AB - Homologous recombination (HR) is a high-fidelity DNA repair pathway responsible for the resolution of double- strand breaks, with the RAD51 recombinase playing a pivotal role through the formation of nucleoprotein fil- aments on single-stranded DNA. Overexpression of RAD51 is frequently observed in cancer cells, where it pro- motes genome stability under genotoxic stress and contributes to acquired resistance to DNA-damaging chemotherapeutic agents. In this study, we report the identification of a novel stilbene-derived compound, the disodium salt of 4,4′-diphenylcarbamate stilbene-2,2′-disulfonic acid (DPDS), as a novel compound that modu- lates RAD51 monomer–monomer interactions and reduces its binding to single-stranded DNA and ATP, processes that are critical for filament assembly and homologous recombination. Furthermore, DPDS enhances the cyto- toxic effect of cisplatin in DU145 prostate cancer cells and was associated with reduced RAD51 nuclear foci formation and increased accumulation of DNA double-strand breaks. Notably, DPDS did not significantly affect cell viability in the four cellular models evaluated under our experimental conditions and displayed lower intrinsic cytotoxicity than DIDS (4,4′-diisothiocyanostilbene-2,2′-disulfonic acid) and emzadirib. Collectively, these findings support that DPDS as a chemical modulator of RAD51 activity may enhance cisplatin sensitivity in DU145 prostate cancer cells.
SN - 0006-2952
SN - 1873-2968
ER -