ArticlePloS one2014
Pemetrexed induces S-phase arrest and apoptosis via a deregulated activation of Akt signaling pathway.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 43 citations in OpenAlex.
- Successful long-term outcome of neoadjuvant sequential targeted therapy and chemotherapy for stage III non-small cell lung carcinoma: 10 case series.Translational lung cancer research · 2024Article
- Phosphodiesterase Inhibition to Sensitize Non-Small-Cell Lung Cancer to Pemetrexed: A Double-Edged Strategy.Cancers · 2024Article
- Lentinan mitigates pemetrexed chemoresistance by the PI3K/Akt pathway in non-small cell lung cancer.Cell biochemistry and biophysics · 2024Article
- CD146 promotes resistance of NSCLC brain metastases to pemetrexed via the NF-κB signaling pathway.Frontiers in pharmacology · 2024Article
- Retraction: Pemetrexed Induces S-Phase Arrest and Apoptosis via a Deregulated Activation of Akt Signaling Pathway.PloS one · 2024Article
- Sequential Delivery of Novel Triple Drug Combination via Crosslinked Alginate/Lactoferrin Nanohybrids for Enhanced Breast Cancer Treatment.Pharmaceutics · 2022Article
- Review
- Restoration of MiR-34a Expression by 5-Azacytidine Augments Alimta -Induced Cell Death in Non-Small Lung Cancer Cells by Downregulation of HMG B1, A2 and Bcl-2 Pathway.Cell journal · 2021Article
- Sulforaphane induces S-phase arrest and apoptosis via p53-dependent manner in gastric cancer cells.Scientific reports · 2021Article
- Response of Human Glioblastoma Cells to Vitamin B12 Deficiency: A Study Using the Non-Toxic Cobalamin Antagonist.Biology · 2021Article
- A WEE1 family business: regulation of mitosis, cancer progression, and therapeutic target.Journal of hematology & oncology · 2020Review
- Accumulated cytotoxicity of CDK inhibitor dinaciclib with first-line chemotherapy drugs in salivary adenoid cystic carcinoma cells.Odontology · 2020Article
- Article
- The deubiquitinating enzyme UCHL1 promotes resistance to pemetrexed in non-small cell lung cancer by upregulating thymidylate synthase.Theranostics · 2020Article
- TIPE2 Induced the Proliferation, Survival, and Migration of Lung Cancer Cells Through Modulation of Akt/mTOR/NF-κB Signaling Cascade.Biomolecules · 2019Article
- Optimal Scheduling of Bevacizumab and Pemetrexed/Cisplatin Dosing in Non-Small Cell Lung Cancer.CPT: pharmacometrics & systems pharmacology · 2019Article
- Exceptional pemetrexed sensitivity can predict therapeutic benefit from subsequent chemotherapy in metastatic non-squamous non-small cell lung cancer.Journal of cancer research and clinical oncology · 2019Article
- Cytostatic and Anti-tumor Potential of Ajwa Date Pulp against Human Hepatocellular Carcinoma HepG2 Cells.Scientific reports · 2019Article
- Article
- Synergistic anti-tumor effect of bullfrog sialic acid-binding lectin and pemetrexed in malignant mesothelioma.Oncotarget · 2017Article
Corrections and comments
- Retraction · 2024-12-13Concerns/Issues about Data · Concerns/Issues about Image · Duplication of Data · Duplication of/in Article · Duplication of/in Image · Euphemisms for Duplication · Objections by Author(s) · Unreliable Results and/or Conclusions ·
- Retracted
Authors and funding
8 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pemetrexed is approved for first-line and maintenance treatment of patients with advanced or metastatic non-small-cell lung cancer (NSCLC). The protein kinase Akt/protein kinase B is a well-known regulator of cell survival which is activated by pemetrexed, but its role in pemetrexed-mediated cell death and its molecular mechanisms are unclear. This study showed that stimulation with pemetrexed induced S-phase arrest and cell apoptosis and a parallel increase in sustained Akt phosphorylation and nuclear accumulation in the NSCLC A549 cell line. Inhibition of Akt expression by Akt specific siRNA blocked S-phase arrest and protected cells from apoptosis, indicating an unexpected proapoptotic role of Akt in the pemetrexed-mediated toxicity. Treatment of A549 cells with pharmacological inhibitors of phosphatidylinositol 3-kinase (PI3K), wortmannin and Ly294002, similarly inhibited pemetrexed-induced S-phase arrest and apoptosis and Akt phosphorylation, indicating that PI3K is an upstream mediator of Akt and is involved in pemetrexed-mediated cell death. Previously, we identified cyclin A-associated cyclin-dependent kinase 2 (Cdk2) as the principal kinase that was required for pemetrexed-induced S-phase arrest and apoptosis. The current study showed that inhibition of Akt function and expression by pharmacological inhibitors as well as Akt siRNA drastically inhibited cyclin A/Cdk2 activation. These pemetrexed-mediated biological and molecular events were also observed in a H1299 cell line. Overall, our results indicate that, in contrast to its normal prosurvival role, the activated Akt plays a proapoptotic role in pemetrexed-mediated S-phase arrest and cell death through a mechanism that involves Cdk2/cyclin A activation.
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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.