ArticleOncoscience2015
Mcl-1 protects prostate cancer cells from cell death mediated by chemotherapy-induced DNA damage.
Article in Oncoscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
27 citing papers in PubMed, 45 citations in OpenAlex.
- Developing therapeutic strategies to target MCL1 and BCLXL in lethal prostate cancer.iScience · 2025Article
- Elucidating molecularly stratified single agent, and combination, therapeutic strategies targeting MCL1 for lethal prostate cancer.Nature communications · 2025Article
- Article
- A Novel Chemotherapy Combination to Enhance Proteotoxic Cell Death in Hepatocellular Carcinoma Experimental Models Without Killing Non-Cancer Cells.International journal of molecular sciences · 2025Article
- Castrate-resistant prostate cancer response to taxane is determined by an HNF1-dependent apoptosis resistance circuit.Cell reports. Medicine · 2024Article
- Orexins and Prostate Cancer: State of the Art and Potential Experimental and Therapeutic Perspectives.Cancer genomics & proteomics · 2023Review
- 5,6-Dichloro-1-β-D-ribofuranosylbenzimidazole (DRB) induces apoptosis in breast cancer cells through inhibiting of Mcl-1 expression.Scientific reports · 2023Article
- Inducing apoptosis by using microRNA in radio-resistant prostate cancer: an in-silico study with an in-vitro validation.Molecular biology reports · 2023Article
- Article
- Article
- Patchouli alcohol suppresses castration-resistant prostate cancer progression by inhibiting NF-κB signal pathways.Translational andrology and urology · 2022Article
- Stem Extract fromMolecules (Basel, Switzerland) · 2022Article
- Fibronectin Modulates the Expression of miRNAs in Prostate Cancer Cell Lines.Frontiers in veterinary science · 2022Article
- Synergism of a novel MCL‑1 downregulator, acriflavine, with navitoclax (ABT‑263) in triple‑negative breast cancer, lung adenocarcinoma and glioblastoma multiforme.International journal of oncology · 2022Article
- Myeloid cell leukemia-1: a formidable barrier to anticancer therapeutics and the quest of targeting it.Exploration of targeted anti-tumor therapy · 2022Review
- Targeting the Intrinsic Apoptosis Pathway: A Window of Opportunity for Prostate Cancer.Cancers · 2021Review
- A Review on Preparation of Betulinic Acid and Its Biological Activities.Molecules (Basel, Switzerland) · 2021Review
- Article
- Inhibition of Anti-Apoptotic Bcl-2 Proteins in Preclinical and Clinical Studies: Current Overview in Cancer.Cells · 2020Review
- Honokiol Suppressed Pancreatic Cancer Progression via miR-101/Mcl-1 Axis.Cancer management and research · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The anti-apoptotic protein Mcl-1 is highly expressed in castration-resistant prostate cancer (CRPC), resulting in resistance to apoptosis and association with poor prognosis. Although predominantly localized in the cytoplasm, there is evidence that Mcl-1 exhibits nuclear localization where it is thought to protect against DNA damage-induced cell death. The role of Mcl-1 in mediating resistance to chemotherapy-induced DNA damage in prostate cancer (PCa) is not known. We show in human PCa cell lines and in TRAMP, a transgenic mouse model of PCa, that the combination of the antimitotic agent ENMD-1198 (analog of 2-methoxyestradiol) with betulinic acid (BA, increases proteotoxic stress) targets Mcl-1 by increasing its proteasomal degradation, resulting in increased γH2AX (DNA damage) and apoptotic/necrotic cell death. Knockdown of Mcl-1 in CRPC cells leads to elevated γH2AX, DNA strand breaks, and cell death after treatment with 1198 + BA- or doxorubicin. Additional knockdowns in PC3 cells suggests that cytoplasmic Mcl-1 protects against DNA damage by blocking the mitochondrial release of apoptosis-inducing factor and thereby preventing its nuclear translocation and subsequent interaction with the cyclophilin A endonuclease. Overall, our results suggest that chemotherapeutic agents that target Mcl-1 will promote cell death in response to DNA damage, particularly in CRPC.
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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.