ArticleBMC cancer2013
Potentiation of in vitro and in vivo antitumor efficacy of doxorubicin by cyclin-dependent kinase inhibitor P276-00 in human non-small cell lung cancer cells.
Article in BMC cancer, 2013. 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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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
18 citing papers in PubMed, 40 citations in OpenAlex.
- A phase II, single-arm, open-label, multicenter study to evaluate the efficacy and safety of P276-00, a cyclin-dependent kinase inhibitor, in patients with relapsed or refractory mantle cell lymphoma.Clinical lymphoma, myeloma & leukemia · 2015Trial
- Ethyl acetate extract ofResearch in pharmaceutical sciences · 2026Article
- Reframing Triazoloacridinone C-1305 as a G-Quadruplex Pharmacophore.The journal of physical chemistry. B · 2026Article
- Combination of the First-in-Class Imipridone ONC201 and Standard Anticancer Therapies as a Rational Approach for Therapeutic Benefit.Current issues in molecular biology · 2025Review
- 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
- Biogenically synthesized gold nanocarrier ameliorated antiproliferative and apoptotic efficacy of doxorubicin against lung cancer.Frontiers in pharmacology · 2024Article
- A Synergistic pH-Responsive Serum Albumin-Based Drug Delivery System Loaded with Doxorubicin and Pentacyclic Triterpene Betulinic Acid for Potential Treatment of NSCLC.Biotech (Basel (Switzerland)) · 2023Article
- CDK9 inhibitors in multiple myeloma: a review of progress and perspectives.Medical oncology (Northwood, London, England) · 2022Review
- Multicellular Effects of STAT3 in Non-small Cell Lung Cancer: Mechanistic Insights and Therapeutic Opportunities.Cancers · 2021Review
- The Involvement of the Oxidative Stress Status in Cancer Pathology: A Double View on the Role of the Antioxidants.Oxidative medicine and cellular longevity · 2021Review
- Inhibition of cyclin-dependent kinase 2 protects against doxorubicin-induced cardiomyocyte apoptosis and cardiomyopathy.The Journal of biological chemistry · 2018Article
- G2/M inhibitors as pharmacotherapeutic opportunities for glioblastoma: the old, the new, and the future.Cancer biology & medicine · 2018Article
- Reactive oxygen species-driven mitochondrial injury induces apoptosis by teroxirone in human non-small cell lung cancer cells.Oncology letters · 2017Article
- Farnesiferol c induces apoptosis via regulation of L11 and c-Myc with combinational potential with anticancer drugs in non-small-cell lung cancers.Scientific reports · 2016Article
- TAB3 overexpression promotes cell proliferation in non-small cell lung cancer and mediates chemoresistance to CDDP in A549 cells via the NF-κB pathway.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Targeting cell cycle regulators in hematologic malignancies.Frontiers in cell and developmental biology · 2015Review
- Liposomal co-delivery of omacetaxine mepesuccinate and doxorubicin for synergistic potentiation of antitumor activity.Pharmaceutical research · 2014Article
- Mussel-inspired protein-mediated surface functionalization of electrospun nanofibers for pH-responsive drug delivery.Acta biomaterialia · 2014Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIn the present study, we show that the combination of doxorubicin with the cyclin-dependent kinase inhibitor P276-00 was synergistic at suboptimal doses in the non-small cell lung carcinoma (NSCLC) cell lines and induces extensive apoptosis than either drug alone in H-460 human NSCLC cells.
methodsSynergistic effects of P276-00 and doxorubicin on growth inhibition was studied using the Propidium Iodide (PI) assay. The doses showing the best synergistic effect was determined and these doses were used for further mechanistic studies such as western blotting, cell cycle analysis and RT-PCR. The in vivo efficacy of the combination was evaluated using the H-460 xenograft model.
resultsThe combination of 100 nM doxorubicin followed by 1200 nM P276-00 showed synergistic effect in the p53-positive and p53-mutated cell lines H-460 and H23 respectively as compared to the p53-null cell line H1299. Abrogation of doxorubicin-induced G2/M arrest and induction of apoptosis was observed in the combination treatment. This was associated with induction of tumor suppressor protein p53 and reduction of anti-apoptotic protein Bcl-2. Furthermore, doxorubicin alone greatly induced COX-2, a NF-κB target and Cdk-1, a target of P276-00, which was downregulated by P276-00 in the combination. Doxorubicin when combined with P276-00 in a sequence-specific manner significantly inhibited tumor growth, compared with either doxorubicin or P276-00 alone in H-460 xenograft model.
conclusionThese findings suggest that this combination may increase the therapeutic index over doxorubicin alone and reduce systemic toxicity of doxorubicin most likely via an inhibition of doxorubicin-induced chemoresistance involving NF-κB signaling and inhibition of Cdk-1 which is involved in cell cycle progression.
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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.