ArticleInternational journal of molecular sciences2019
Obatoclax, a BH3 Mimetic, Enhances Cisplatin-Induced Apoptosis and Decreases the Clonogenicity of Muscle Invasive Bladder Cancer Cells via Mechanisms That Involve the Inhibition of Pro-Survival Molecules as Well as Cell Cycle Regulators.
Article in International journal of molecular sciences, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 22 citations in OpenAlex.
- Dual targeting of BCL-XL and MCL-1 exposes a rapid and exploitable apoptotic vulnerability in non-small cell lung cancer.Cell death and differentiation · 2026Article
- Atypical cadherin FAT1 promotes tumorigenesis by suppressing autophagic cell death in glioblastoma under hypoxia or nutrient stress.Cellular & molecular biology letters · 2025Article
- Promising Prodiginins Biological Activities.Chemistry & biodiversity · 2025Review
- Development of a Bladder Cancer-on-a-Chip Model to Assess Bladder Cancer Cell Invasiveness.Cancers · 2024Article
- Mitochondria of T Lymphocytes Promote Anti-Pulmonary Tumor Immune Response.World journal of oncology · 2024Article
- Review
- The construction of a prognostic model of cervical cancer based on four immune-related LncRNAs and an exploration of the correlations between the model and oxidative stress.Frontiers in pharmacology · 2023Article
- Article
- Systems Drug Design for Muscle Invasive Bladder Cancer and Advanced Bladder Cancer by Genome-Wide Microarray Data and Deep Learning Method with Drug Design Specifications.International journal of molecular sciences · 2022Article
- Computational design of an apoptogenic protein that binds BCL-xL and MCL-1 simultaneously and potently.Computational and structural biotechnology journal · 2022Article
- NXPH4 Used as a New Prognostic and Immunotherapeutic Marker for Muscle-Invasive Bladder Cancer.Journal of oncology · 2022Article
- BH3-mimetics: recent developments in cancer therapy.Journal of experimental & clinical cancer research : CR · 2021Review
- Discovery, development and application of drugs targeting BCL-2 pro-survival proteins in cancer.Biochemical Society transactions · 2021Review
- Review
- Obatoclax, a Pan-BCL-2 Inhibitor, Downregulates Survivin to Induce Apoptosis in Human Colorectal Carcinoma Cells Via Suppressing WNT/β-catenin Signaling.International journal of molecular sciences · 2020Article
- Novel Combination Therapies for the Treatment of Bladder Cancer.Frontiers in oncology · 2020Review
- Special Issue on Molecular Research Efforts in Urothelial Carcinoma: Summary of Included Topics.International journal of molecular sciences · 2019Article
- Mitochondrial determinants of chemoresistance.Cancer drug resistance (Alhambra, Calif.) · 2019Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Several studies by our group and others have determined that expression levels of Bcl-2 and/or Bcl-xL, pro-survival molecules which are associated with chemoresistance, are elevated in patients with muscle invasive bladder cancer (MI-BC). The goal of this study was to determine whether combining Obatoclax, a BH3 mimetic which inhibits pro-survival Bcl-2 family members, can improve responses to cisplatin chemotherapy, the standard of care treatment for MI-BC. Three MI-BC cell lines (T24, TCCSuP, 5637) were treated with Obatoclax alone or in combination with cisplatin and/or pre-miR-34a, a molecule which we have previously shown to inhibit MI-BC cell proliferation via decreasing Cdk6 expression. Proliferation, clonogenic, and apoptosis assays confirmed that Obatoclax can decrease cell proliferation and promote apoptosis in a dose-dependent manner. Combination treatment experiments identified Obatoclax + cisplatin as the most effective treatment. Immunoprecipitation and Western analyses indicate that, in addition to being able to inhibit Bcl-2 and Bcl-xL, Obatoclax can also decrease cyclin D1 and Cdk4/6 expression levels. This has not previously been reported. The combined data demonstrate that Obatoclax can inhibit cell proliferation, promote apoptosis, and significantly enhance the effectiveness of cisplatin in MI-BC cells via mechanisms that likely involve the inhibition of both pro-survival molecules and cell cycle regulators.
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Registered trials
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.