SeSA-HCPT: A dual-targeting agent that induces DNA damage and inhibits repair for castration-resistant prostate cancer therapy
Yajie Wang, Qiuyu Wang, Li Meng, Xiaoying Lian, Xinyue Wu, Yuqing Wang, Tianyu Zhang, ShiLin Wei, Yanming Wang, Changjun Zhu
TL;DR
SeSA-HCPT is a new drug that targets two pathways in prostate cancer cells, causing DNA damage and preventing repair, which could lead to better treatment for advanced prostate cancer.
Contribution
SeSA-HCPT is a novel dual-targeting agent combining Topo I and HDAC inhibition for prostate cancer therapy.
Findings
SeSA-HCPT showed higher cytotoxicity in prostate cancer cells than single or combined treatments.
It induced DNA damage and S-phase arrest while suppressing homologous recombination repair.
Oral SeSA-HCPT inhibited tumor growth in a xenograft model with minimal toxicity.
Abstract
Castration-resistant prostate cancer (CRPC) remains difficult to treat due to tumor heterogeneity and resistance. We developed SeSA-HCPT, a dual-targeting compound that links the topoisomerase I inhibitor hydroxycamptothecin (HCPT) with a selenium analog of the histone deacetylase (HDAC) inhibitor suberoylanilide hydroxamic acid. SeSA-HCPT showed markedly higher cytotoxicity in prostate cancer (PCa) cells than single or combined treatments, while sparing normal keratinocytes. At effective concentrations, it triggered pronounced S-phase arrest and apoptosis, driven by Topo I inhibition and extensive DNA double-strand breaks; concurrently, SeSA-HCPT suppressed homologous recombination through downregulation of KIF4A and impaired RAD51 recruitment. In a PC-3 xenograft model, SeSA-HCPT significantly inhibited tumor growth relative to the combination treatment without observable systemic…
Genes, proteins, chemicals, diseases, species, mutations and cell lines named across the full text — each resolved to its canonical identifier and authoritative record.
Click any figure to enlarge with its caption.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Figure 9Peer Reviews
No public reviews on file for this paper yet. If you reviewed it on a platform where reviews are public (OpenReview, ICLR, NeurIPS, ICML), you can paste yours below so the community can read it here.
Videos
No videos yet. Explain this paper in a talk, walkthrough, or lecture? Add one.
Taxonomy
TopicsProstate Cancer Treatment and Research · Histone Deacetylase Inhibitors Research · Cancer therapeutics and mechanisms