Dataset Information

Drug library screening identifies histone deacetylase inhibition as a novel therapeutic strategy for choriocarcinoma.

ABSTRACT:

Background

Choriocarcinoma 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.

Methods

Three 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.

Results

Muti-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.

Conclusion

Vorinostat, 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.

SUBMITTER: Watanabe E

PROVIDER: S-EPMC9972027 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Drug library screening identifies histone deacetylase inhibition as a novel therapeutic strategy for choriocarcinoma.

Watanabe Eri E Yokoi Akira A Yoshida Kosuke K Sugiyama Mai M Kitagawa Masami M Nishino Kimihiro K Yamamoto Eiko E Niimi Kaoru K Yamamoto Yusuke Y Kajiyama Hiroaki H

Cancer medicine 20220915 4

<h4>Background</h4>Choriocarcinoma 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.<h4>Methods</h4>Three choriocarcinoma cell lines (JAR, JEG-3, and BeWo) and a human extravillous ...[more]

PMID: 36106577

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Dataset Information

Drug library screening identifies histone deacetylase inhibition as a novel therapeutic strategy for choriocarcinoma.

Background

Methods

Results

Conclusion

Publications

Drug library screening identifies histone deacetylase inhibition as a novel therapeutic strategy for choriocarcinoma.

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