ArticleScientific reports2016
Next-generation proteasome inhibitor MLN9708 sensitizes breast cancer cells to doxorubicin-induced apoptosis.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 48 citations in OpenAlex.
- Trial
- USP51/GRP78/ABCB1 axis confers chemoresistance through decreasing doxorubicin accumulation in triple-negative breast cancer cells.Acta pharmaceutica Sinica. B · 2025Article
- Caspase 3 and caspase 7 promote cytoprotective autophagy and the DNA damage response during non-lethal stress conditions in human breast cancer cells.PLoS biology · 2025Article
- Ubiquitination regulates autophagy in cancer: simple modifications, promising targets.Journal of translational medicine · 2024Review
- Review
- Article
- Long non-coding RNAs as the critical regulators of PI3K/AKT, TGF-β, and MAPK signaling pathways during breast tumor progression.Journal of translational medicine · 2023Review
- Nanomedicine for autophagy modulation in cancer therapy: a clinical perspective.Cell & bioscience · 2023Review
- DNMT2/TRDMT1 gene knockout compromises doxorubicin-induced unfolded protein response and sensitizes cancer cells to ER stress-induced apoptosis.Apoptosis : an international journal on programmed cell death · 2023Article
- Rational drug combination design in patient-derived avatars reveals effective inhibition of hepatocellular carcinoma with proteasome and CDK inhibitors.Journal of experimental & clinical cancer research : CR · 2022Article
- Screening and identification of HTNVVirologica Sinica · 2022Article
- Dormancy in Breast Cancer, the Role of Autophagy, lncRNAs, miRNAs and Exosomes.International journal of molecular sciences · 2022Review
- Autophagy, Oxidative Stress and Cancer Development.Cancers · 2022Review
- p62 Promotes the Mitochondrial Localization of p53 through Its UBA Domain and Participates in Regulating the Sensitivity of Ovarian Cancer Cells to Cisplatin.International journal of molecular sciences · 2022Article
- Production of Epoxyketone Peptide-Based Proteasome Inhibitors byFrontiers in microbiology · 2022Article
- Does the proteasome inhibitor bortezomib sensitize to DNA-damaging therapy in gastroenteropancreatic neuroendocrine neoplasms? - A preclinical assessment in vitro and in vivo.Neoplasia (New York, N.Y.) · 2021Article
- Article
- BET Inhibitors Synergize with Carfilzomib to Induce Cell Death in Cancer Cells via Impairing Nrf1 Transcriptional Activity and Exacerbating the Unfolded Protein Response.Biomolecules · 2020Article
- Knockdown of lncRNA-HOTAIR downregulates the drug-resistance of breast cancer cells to doxorubicin via the PI3K/AKT/mTOR signaling pathway.Experimental and therapeutic medicine · 2019Article
- Delanzomib, a novel proteasome inhibitor, sensitizes breast cancer cells to doxorubicin-induced apoptosis.Thoracic cancer · 2019Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Doxorubicin (Dox), one of the most effective chemotherapy drug for cancer treatment, is limited by its severe side effects and chemoresistance. Dox induces DNA damage and leads to significant proteomic changes in the cancer cells, which makes the ubiquitin-proteasome system a potential target to enhance the efficacy of Dox therapy. The unsuccessful clinical trials of proteasome inhibitor PS-341 (bortezomib) in solid tumors led to the invention of MLN9708 (ixazomib), an orally bioavailable next-generation proteasome inhibitor with improved pharmacokinetic and pharmacodynamic features. In this preclinical study, we used eight human breast cancer cell lines, which represent the major molecular subtypes of breast cancer, to validate the cytotoxic effects of MLN9708, alone and in combination with Dox. We found that MLN9708 had cytotoxic effects, induced autophagy and MKP-1 expression, and enhanced Dox-induced apoptosis in these cell lines. MLN9708 also enhanced Dox-induced JNK and p38 phosphorylation and inhibited Dox-induced IκBα degradation. Our in vitro results suggest that MLN9708 has antitumor effects in breast cancer and can sensitize breast cancer cells to Dox treatment. This promising combination may be an effective and feasible therapeutic option for treating breast cancer and warrants clinical validation.
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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.