ArticleMolecular cancer therapeutics2010
PUMA induction by FoxO3a mediates the anticancer activities of the broad-range kinase inhibitor UCN-01.
Article in Molecular cancer therapeutics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 67 citations in OpenAlex.
- The multifaceted role of PUMA in cell death pathways: its therapeutic potential across cancer types.Cell communication and signaling : CCS · 2025Review
- Depletion of oxysterol-binding proteins by OSW-1 triggers RIP1/RIP3-independent necroptosis and sensitization to cancer immunotherapy.Cell death and differentiation · 2025Article
- Measuring FOXO Activity by Using qPCR-Based Expression Analysis of FOXO Target Genes.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Inhibition of multiple CDKs potentiates colon cancer chemotherapy via p73-mediated DR5 induction.Oncogene · 2023Article
- Synthetical lethality of Werner helicase and mismatch repair deficiency is mediated by p53 and PUMA in colon cancer.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Nicotine-induced miR-21-3p promotes chemoresistance in lung cancer by negatively regulating FOXO3a.Oncology letters · 2022Article
- Article
- Identification of a Novel Immune Landscape Signature for Predicting Prognosis and Response of Colon Cancer to Immunotherapy.Frontiers in immunology · 2022Article
- BRD9 inhibition promotes PUMA-dependent apoptosis and augments the effect of imatinib in gastrointestinal stromal tumors.Cell death & disease · 2021Article
- P53-independent partial restoration of the p53 pathway in tumors with mutated p53 through ATF4 transcriptional modulation by ERK1/2 and CDK9.Neoplasia (New York, N.Y.) · 2021Article
- Mechanisms of resistance to FGFR1 inhibitors in FGFR1-driven leukemias and lymphomas: implications for optimized treatment.Cancer drug resistance (Alhambra, Calif.) · 2021Article
- Identification prognosis-associated immune genes in colon adenocarcinoma.Bioscience reports · 2020Article
- Downregulation of PUMA underlies resistance to FGFR1 inhibitors in the stem cell leukemia/lymphoma syndrome.Cell death & disease · 2020Article
- Pristimerin-induced uveal melanoma cell death via inhibiting PI3K/Akt/FoxO3a signalling pathway.Journal of cellular and molecular medicine · 2020Article
- Targeting mTOR suppressed colon cancer growth through 4EBP1/eIF4E/PUMA pathway.Cancer gene therapy · 2020Article
- Purified vitexin compound 1, a new neolignan isolated compound, promotes PUMA-dependent apoptosis in colorectal cancer.Cancer medicine · 2018Article
- Inhibition of kinesin family member 20B sensitizes hepatocellular carcinoma cell to microtubule-targeting agents by blocking cytokinesis.Cancer science · 2018Article
- MEK inhibitors induce apoptosis via FoxO3a-dependent PUMA induction in colorectal cancer cells.Oncogenesis · 2018Article
- Reducing protein regulator of cytokinesis 1 as a prospective therapy for hepatocellular carcinoma.Cell death & disease · 2018Article
- PUMA amplifies necroptosis signaling by activating cytosolic DNA sensors.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Most targeted anticancer drugs are inhibitors of kinases that are aberrantly activated in cancer cells. However, the mechanisms by which kinase inhibitors suppress tumor growth remain unclear. In this study, we found that UCN-01, a staurosporine analogue and broad-range kinase inhibitor used in clinical trials, inhibits colon cancer cell growth by inducing apoptosis via PUMA, a BH3-only Bcl-2 family member and a p53 target. PUMA expression was markedly elevated in a p53-independent fashion following UCN-01 treatment. The induction of PUMA by UCN-01 was mediated by direct binding of FoxO3a to the PUMA promoter following inhibition of AKT signaling. Deficiency in PUMA abrogated UCN-01-induced apoptosis, caspase activation, and mitochondrial dysfunction, and rendered UCN-01 resistance in a clonogenic assay, whereas elevated PUMA expression or a BH3 mimetic sensitized UCN-01 induced apoptosis. Chemosensitization by UCN-01 seemed to involve simultaneous PUMA induction through both p53-dependent and p53-independent mechanisms. Furthermore, deficiency in PUMA suppressed the antitumor effects of UCN-01 in a xenograft model, concurrent with reduced apoptosis and caspase activation in vivo. These results suggest that PUMA-mediated apoptosis is pivotal for the anticancer activities of UCN-01, and possibly other clinically used kinase inhibitor drugs, and that PUMA manipulation may be useful for improving their anticancer activities.
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