ArticleCancer medicine2023
Drug library screening identifies histone deacetylase inhibition as a novel therapeutic strategy for choriocarcinoma.
Article in Cancer medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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6 citing papers in PubMed, 14 citations in OpenAlex.
- Panobinostat potentiates adagrasib-induced cell death by triggering autophagy in human non-small cell lung cancer.Cell death discovery · 2025Article
- Article
- Non-coding RNAs in the spotlight of the pathogenesis, diagnosis, and therapy of cutaneous T cell lymphoma.Cell death discovery · 2024Review
- Transcriptomic comparison of in vitro models of the human placenta.bioRxiv : the preprint server for biology · 2024Article
- Establishment and characterization of a non-gestational choriocarcinoma patient-derived xenograft model.BMC cancer · 2023Article
- Design, Synthesis, and Biological Evaluation of Novel Quinazolin-4(3H)-One-Based Histone Deacetylase 6 (HDAC6) Inhibitors for Anticancer Activity.International journal of molecular sciences · 2023Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundChoriocarcinoma is a rare and aggressive gynecological malignancy. The standard treatment is systemic chemotherapy as choriocarcinoma exhibits high chemosensitivity. However, refractory choriocarcinoma exhibits chemoresistance; thus, the prognosis remains very poor. This study aimed to identify novel therapeutic agents for choriocarcinoma by utilizing a drug repositioning strategy.
methodsThree choriocarcinoma cell lines (JAR, JEG-3, and BeWo) and a human extravillous trophoblast cell line (HTR-8/SVneo) were used for the analyses. The growth inhibitory effects of 1,271 FDA-approved compounds were evaluated in vitro screening assays and selected drugs were tested in tumor-bearing mice. Functional analyses of drug effects were performed based on RNA sequencing.
resultsMuti-step screening identified vorinostat, camptothecin (S, +), topotecan, proscillaridin A, and digoxin as exhibiting an anti-cancer effect in choriocarcinoma cells. Vorinostat, a histone deacetylase inhibitor, was selected as a promising candidate for validation and the IC50 values for choriocarcinoma cells were approximately 1 μM. RNA sequencing and subsequent pathway analysis revealed that the ferroptosis pathway was likely implicated, and key ferroptosis-related genes (i.e., GPX4, NRF2, and SLC3A2) were downregulated following vorinostat treatment. Furthermore, vorinostat repressed tumor growth and downregulated the expression of GPX4 and NRF2 in JAR cell-bearing mice model.
conclusionVorinostat, a clinically approved drug for the treatment of advanced primary cutaneous T-cell lymphoma, showed a remarkable anticancer effect both in vitro and in vivo by regulating the expression of ferroptosis-related genes. Therefore, vorinostat may be an effective therapeutic candidate for patients with choriocarcinoma.
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