ArticleInternational journal of molecular sciences2018
5-Azacitidine Exerts Prolonged Pro-Apoptotic Effects and Overcomes Cisplatin-Resistance in Non-Seminomatous Germ Cell Tumor Cells.
Article in International journal of molecular sciences, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 66 citations in OpenAlex.
- Driving precision medicine in testicular germ cell tumors: from preclinical models to clinical applications.Therapeutic advances in medical oncology · 2026Review
- Treatment options in platinum-refractory male germ cell cancers: current standards and future directions.Therapeutic advances in medical oncology · 2026Review
- Epigenetic mechanisms in maternal-fetal crosstalk: inter- and trans-generational inheritance.Epigenomics · 2025Review
- Review
- Mechanisms of cisplatin sensitivity and resistance in testicular germ cell tumors and potential therapeutic agents (Review).Experimental and therapeutic medicine · 2025Review
- Refractory testicular germ cell tumors are highly sensitive to the targeting of polycomb pathway demethylases KDM6A and KDM6B.Cell communication and signaling : CCS · 2024Article
- Recent Advancements in Research on DNA Methylation and Testicular Germ Cell Tumors: Unveiling the Intricate Relationship.Biomedicines · 2024Review
- Novel meriolin derivatives activate the mitochondrial apoptosis pathway in the presence of antiapoptotic Bcl-2.Cell death discovery · 2024Article
- A functional personalised oncology approach against metastatic colorectal cancer in matched patient derived organoids.NPJ precision oncology · 2024Article
- Breaking the Mold: Epigenetics and Genomics Approaches Addressing Novel Treatments and Chemoresponse in TGCT Patients.International journal of molecular sciences · 2023Review
- Epigenetic Regulation of Driver Genes in Testicular Tumorigenesis.International journal of molecular sciences · 2023Review
- Overcoming Chemotherapy Resistance in Germ Cell Tumors.Biomedicines · 2022Review
- DNA Methylation Malleability and Dysregulation in Cancer Progression: Understanding the Role of PARP1.Biomolecules · 2022Review
- Reciprocal epigenetic remodeling controls testicular cancer hypersensitivity to hypomethylating agents and chemotherapy.Molecular oncology · 2022Article
- Therapeutical interference with the epigenetic landscape of germ cell tumors: a comparative drug study and new mechanistical insights.Clinical epigenetics · 2022Article
- Radiotherapy role in non-seminomatous germ cell tumors, radiobiological and technical issues of an unexplored scenario.International journal of clinical oncology · 2021Review
- Hypermethylation and global remodelling of DNA methylation is associated with acquired cisplatin resistance in testicular germ cell tumours.Epigenetics · 2021Article
- Article
- Differential methylation EPIC analysis discloses cisplatin-resistance related hypermethylation and tumor-specific heterogeneity within matched primary and metastatic testicular germ cell tumor patient tissue samples.Clinical epigenetics · 2021Article
- Promoter methylation of DNA homologous recombination genes is predictive of the responsiveness to PARP inhibitor treatment in testicular germ cell tumors.Molecular oncology · 2021Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite high cure rates, about 20% of patients with advanced germ cell tumors (GCTs) fail cisplatin-based chemotherapy. High levels of DNA methylation have been identified in GCTs and linked to cisplatin resistance. Here, we examined the effects of DNA hypomethylating 5-azacitidine (5-aza) on two embryonal carcinoma cell lines (NCCIT, 2102Ep) and their cisplatin-resistant isogenic derivatives. Effects on cell viability and cisplatin sensitivity were assessed by the trypan blue exclusion method. Western blotting was used to examine induction of apoptosis 5-aza and results were validated by flow cytometry. Single agent treatment with 5-aza strongly impacted viability and induced apoptosis at low nanomolar concentrations, both in cisplatin-sensitive and -resistant cell lines. 5-aza exerted an immediate apoptotic response, followed by a prolonged inhibitory effect on cell viability and cell-cycle progression. Sequential treatment with 5-aza and cisplatin reduced cellular survival of the cisplatin-resistant sublines already at nanomolar concentrations, suggesting a partial restoration of cisplatin sensitivity by the compound. 5-aza demonstrated anti-tumor activity as a single agent at low nanomolar concentrations in GCT cells, irrespective of cisplatin-sensitivity. 5-aza may also have the potential at least to partially restore cisplatin-sensitivity in non-seminoma cells, supporting the hypothesis that combining DNA demethylating agents with cisplatin-based chemotherapy may be a valid therapeutic approach in patients with refractory GCTs.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.