ArticleMolecular therapy : the journal of the American Society of Gene Therapy2013
BCL-2 inhibitors sensitize therapy-resistant chronic lymphocytic leukemia cells to VSV oncolysis.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 31 citations in OpenAlex.
- Therapeutic potential of oncolytic viruses in hematopoietic malignancies: from preclinical insights to clinical realities.Frontiers in microbiology · 2026Review
- Measles Virus-Based Genetic Modifications: Progress in Hematological Malignancy Treatment.OncoTargets and therapy · 2025Review
- Zinc Oxide Nanoparticles Induce Renal Injury by Initiating Oxidative Stress, Mitochondrial Damage and Apoptosis in Renal Tubular Epithelial Cells.Biological trace element research · 2024Article
- Identification of an Autophagy-Related lncRNA Prognostic Signature and Related Tumor Immunity Research in Lung Adenocarcinoma.Frontiers in genetics · 2021Article
- The Role of Vesicular Stomatitis Virus Matrix Protein in Autophagy in the Breast Cancer.Asian Pacific journal of cancer prevention : APJCP · 2021Article
- Efficient Delivery and Replication of Oncolytic Virus for Successful Treatment of Head and Neck Cancer.International journal of molecular sciences · 2020Review
- Chemical, Physical and Biological Triggers of Evolutionary Conserved Bcl-xL-Mediated Apoptosis.Cancers · 2020Article
- Shikonin potentiates paclitaxel antitumor efficacy in esophageal cancer cells via the apoptotic pathway.Oncology letters · 2019Article
- Plasmacytoid dendritic cells orchestrate innate and adaptive anti-tumor immunity induced by oncolytic coxsackievirus A21.Journal for immunotherapy of cancer · 2019Article
- Recent advances in vesicular stomatitis virus-based oncolytic virotherapy: a 5-year update.The Journal of general virology · 2017Article
- Antiviral Properties of Chemical Inhibitors of Cellular Anti-Apoptotic Bcl-2 Proteins.Viruses · 2017Article
- Review
- Murine Tumor Models for Oncolytic Rhabdo-Virotherapy.ILAR journal · 2016Article
- Histone deacetylase inhibitors potentiate vesicular stomatitis virus oncolysis in prostate cancer cells by modulating NF-κB-dependent autophagy.Journal of virology · 2014Article
- Role of high expression of IL-9 in prognosis of CLL.International journal of clinical and experimental pathology · 2014Article
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
Abstract
Many primary cancers including chronic lymphocytic leukemia (CLL) are resistant to vesicular stomatitis virus (VSV)-induced oncolysis due to overexpression of the antiapoptotic and antiautophagic members of the B-cell lymphoma-2 (BCL-2) family. In the present study, we investigated the mechanisms of CLL cell death induced as a consequence of VSV infection in the presence of BCL-2 inhibitors, obatoclax, and ABT-737 in primary ex vivo CLL patient samples. Microarray analysis of primary CD19⁺ CD5⁺ CLL cells treated with obatoclax and VSV revealed changes in expression of genes regulating apoptosis, the mechanistic target of rapamycin (mTOR) pathway, and cellular metabolism. A combined therapeutic effect was observed for VSV and BCL-2 inhibitors in cells from untreated patients and from patients unresponsive to standard of care therapy. In addition, combination treatment induced several markers of autophagy--LC3-II accumulation, p62 degradation, and staining of autophagic vacuoles. Inhibition of early stage autophagy using 3-methyladenine (3-MA) led to increased apoptosis in CLL samples. Mechanistically, a combination of BCL-2 inhibitors and VSV disrupted inhibitory interactions of Beclin-1 with BCL-2 and myeloid cell leukemia-1 (MCL-1), thus biasing cells toward autophagy. We propose a mechanism in which changes in cellular metabolism, coupled with pharmacologic disruption of the BCL-2-Beclin-1 interactions, facilitate induction of apoptosis and autophagy to mediate the cytolytic effect of VSV.
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