ArticleCancer biology & therapy2014
CDK4 inhibition and doxorubicin mediate breast cancer cell apoptosis through Smad3 and survivin.
Article in Cancer biology & therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- Meta analysis of bioactive compounds, miRNA, siRNA and cell death regulators as sensitizers to doxorubicin induced chemoresistance.Apoptosis : an international journal on programmed cell death · 2022Pooled it
- Repurposing a Lipid-Lowering Agent to Inhibit TNBC Growth Through Cell Cycle Arrest.Current issues in molecular biology · 2025Article
- Ribociclib in Sequential Combination with Doxorubicin in Anthracycline-Naïve Advanced Soft-Tissue Sarcomas: Results of a Dose-Finding Phase Ib Study.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Multiomic characterization, immunological and prognostic potential of SMAD3 in pan-cancer and validation in LIHC.Scientific reports · 2025Article
- Article
- Review
- Targeting CDK4 overcomes EMT-mediated tumor heterogeneity and therapeutic resistance in KRAS-mutant lung cancer.JCI insight · 2021Article
- MicroRNA‑198 suppresses tumour growth and metastasis in oral squamous cell carcinoma by targeting CDK4.International journal of oncology · 2021Article
- Cyclin E overexpression confers resistance to trastuzumab through noncanonical phosphorylation of SMAD3 in HER2+ breast cancer.Cancer biology & therapy · 2020Article
- Metformin prevention of doxorubicin resistance in MCF-7 and MDA-MB-231 involves oxidative stress generation and modulation of cell adaptation genes.Scientific reports · 2019Article
- Article
- Estrogen-dependent disruption of intracellular iron metabolism augments the cytotoxic effects of doxorubicin in select breast and ovarian cancer cells.Cancer management and research · 2019Article
- Synergistic effect of eribulin and CDK inhibition for the treatment of triple negative breast cancer.Oncotarget · 2017Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Cyclin D1/CDK4 activity is upregulated in up to 50% of breast cancers and CDK4-mediated phosphorylation negatively regulates the TGFβ superfamily member Smad3. We sought to determine if CDK4 inhibition and doxorubicin chemotherapy could impact Smad3-mediated cell/colony growth and apoptosis in breast cancer cells. Parental and cyclin D1-overexpressing MCF7 cells were treated with CDK4 inhibitor, doxorubicin, or combination therapy and cell proliferation, apoptosis, colony formation, and expression of apoptotic proteins were evaluated using an MTS assay, TUNEL staining, 3D Matrigel assay, and apoptosis array/immunoblotting. Study cells were also transduced with WT Smad3 or a Smad3 construct resistant to CDK4 phosphorylation (5M) and colony formation and expression of apoptotic proteins were assessed. Treatment with CDK4 inhibitor/doxorubicin combination therapy, or transduction with 5M Smad3, resulted in a similar decrease in colony formation. Treating cyclin D overexpressing breast cancer cells with combination therapy also resulted in the greatest increase in apoptosis, resulted in decreased expression of anti-apoptotic proteins survivin and XIAP, and impacted subcellular localization of pro-apoptotic Smac/DIABLO. Additionally, transduction of 5M Smad3 and doxorubicin treatment resulted in the greatest change in apoptotic protein expression. Collectively, this work showed the impact of CDK4 inhibitor-mediated, Smad3-regulated tumor suppression, which was augmented in doxorubicin-treated cyclin D-overexpressing study cells.
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Registered trials
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