ArticleCell death & disease2018
Ipatasertib, a novel Akt inhibitor, induces transcription factor FoxO3a and NF-κB directly regulates PUMA-dependent apoptosis.
Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 96 citations in OpenAlex.
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- Spatial Transcriptomic Atlas Reveals That Forkhead Box O3-Mediated Mitochondrial Dynamics Imbalance Drives Premature Ovarian Insufficiency in Mice.Aging cell · 2026Article
- Review
- Integrated transcriptomic analysis and experimental validation identify ACADL as a mitochondrial tumor suppressor via the FOXO3a/PUMA axis in lung adenocarcinoma.European journal of medical research · 2026Article
- Research progress of small molecule protein kinase inhibitors (SMKIs) in the treatment of colorectal cancer: mechanism, application, and future prospects.Frontiers in pharmacology · 2026Review
- Unraveling the miR-144-3p/PUMA pathway: a novel regulator of FDX1-mediated cuproptosis in colorectal cancer.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- UBE2S inhibits colorectal cancer proliferation by regulating the PI3K/AKT and MAPK/ERK pathways via TRAF6.Scientific reports · 2025Article
- Anti-EGFR Therapy in Metastatic Colorectal Cancer: Identifying, Tracking, and Overcoming Resistance.Cancers · 2025Review
- Targeting the PI3K/AKT/mTOR pathway in lung cancer: mechanisms and therapeutic targeting.Frontiers in pharmacology · 2025Review
- Neuroprotection of IGF-1 in neonatal hypoxic-ischemic brain injury through downregulation of FoXO3a-PUMA pathway.Frontiers in cellular neuroscience · 2025Article
- Potent combination benefit of the AKT inhibitor capivasertib and the BCL-2 inhibitor venetoclax in diffuse large B cell lymphoma.Leukemia · 2024Article
- Interconnection of CD133 Stem Cell Marker with Autophagy and Apoptosis in Colorectal Cancer.International journal of molecular sciences · 2024Review
- Nicotine restores olfactory function by activation of prok2R/Akt/FoxO3a axis in Parkinson's disease.Journal of translational medicine · 2024Article
- Genetic Silencing of AKT Induces Melanoma Cell Death via mTOR Suppression.Molecular cancer therapeutics · 2024Article
- FOXO3a-interacting proteins' involvement in cancer: a review.Molecular biology reports · 2024Review
- Ipatasertib, an oral AKT inhibitor, in combination with carboplatin exhibits anti-proliferative effects in uterine serous carcinoma.Annals of medicine · 2023Article
- Ipatasertib exhibits anti‑tumorigenic effects and enhances sensitivity to paclitaxel in endometrial cancerInternational journal of oncology · 2023Article
- Proteogenomic characterization of ferroptosis regulators reveals therapeutic potential in glioblastoma.BMC cancer · 2023Article
- Contribution of microRNA-30d to the prevention of the thyroid cancer occurrence and progression: mechanism and implications.Apoptosis : an international journal on programmed cell death · 2023Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Colon cancer is one of the three common malignant tumors, with a lower survival rate. Ipatasertib, a novel highly selective ATP-competitive pan-Akt inhibitor, shows a strong antitumor effect in a variety of carcinoma, including colon cancer. However, there is a lack of knowledge about the precise underlying mechanism of clinical therapy for colon cancer. We conducted this study to determine that ipatasertib prevented colon cancer growth through PUMA-dependent apoptosis. Ipatasertib led to p53-independent PUMA activation by inhibiting Akt, thereby activating both FoxO3a and NF-κB synchronously that will directly bind to PUMA promoter, up-regulating PUMA transcription and Bax-mediated intrinsic mitochondrial apoptosis. Remarkably, Akt/FoxO3a/PUMA is the major pathway while Akt/NF-κB/PUMA is the secondary pathway of PUMA activation induced by ipatasertib in colon cancer. Knocking out PUMA eliminated ipatasertib-induced apoptosis both in vitro and in vivo (xenografts). Furthermore, PUMA is also indispensable in combinational therapies of ipatasertib with some conventional or novel drugs. Collectively, our study demonstrated that PUMA induction by FoxO3a and NF-κB is a critical step to suppress the growth of colon cancer under the therapy with ipatasertib, which provides some theoretical basis for clinical assessment.
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