ArticleOncogene2009
9-Aminoacridine-based anticancer drugs target the PI3K/AKT/mTOR, NF-kappaB and p53 pathways.
Article in Oncogene, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 116 citations in OpenAlex.
- Article
- Marine-Derived Steroids for Cancer Treatment: Search for Potential Selective Glucocorticoid Receptor Agonists/Modulators (SEGRAMs).Marine drugs · 2025Review
- Structure-Activity Relationship Investigations Probing the Cytotoxicity of 9-Aminoacridines Derivatives with PC3 and A549.Journal of heterocyclic chemistry · 2024Article
- Influence of N-protonation on electronic properties of acridine derivatives by quantum crystallography.RSC advances · 2024Article
- Developing novel antimicrobials by combining cancer chemotherapeutics with bacterial DNA repair inhibitors.PLoS pathogens · 2023Article
- Talazoparib enhances the quinacrine-mediated apoptosis in patient-derived oral mucosa CSCs by inhibiting BER pathway through the modulation of GCN5 and P300.Medical oncology (Northwood, London, England) · 2023Article
- The drug efficacy testing in 3D cultures platform identifies effective drugs for ovarian cancer patients.NPJ precision oncology · 2023Article
- Repurposing 9-Aminoacridine as an Adjuvant Enhances the Antimicrobial Effects of Rifampin against Multidrug-Resistant Klebsiella pneumoniae.Microbiology spectrum · 2023Article
- Can Zeolite-Supporting Acridines Boost Their Anticancer Performance?Journal of functional biomaterials · 2023Article
- 9-Aminoacridine Inhibits Ribosome Biogenesis by Targeting Both Transcription and Processing of Ribosomal RNA.International journal of molecular sciences · 2022Article
- A 9-aminoacridine derivative induces growth inhibition of Ehrlich ascites carcinoma cells and antinociceptive effect in mice.Frontiers in pharmacology · 2022Article
- An Overview of Novel Agents for Cervical Cancer Treatment by Inducing Apoptosis: Emerging Drugs Ongoing Clinical Trials and Preclinical Studies.Frontiers in medicine · 2021Review
- Genomic and Transcriptome Analysis to Identify the Role of the mTOR Pathway in Kidney Renal Clear Cell Carcinoma and Its Potential Therapeutic Significance.Oxidative medicine and cellular longevity · 2021Article
- Effects of Quinacrine on Expression of Hippo signaling Pathway Components (LATS1, LATS2, and YAP) in Human Breast Cancer Stem Cells.Asian Pacific journal of cancer prevention : APJCP · 2020Article
- The Phenoxyphenol Compound 4-HPPP Selectively Induces Antiproliferation Effects and Apoptosis in Human Lung Cancer Cells through Aneupolyploidization and ATR DNA Repair Signaling.Oxidative medicine and cellular longevity · 2020Article
- A new SIRT1 inhibitor, MHY2245, induces autophagy and inhibits energy metabolism via PKM2/mTOR pathway in human ovarian cancer cells.International journal of biological sciences · 2020Article
- Quinacrine-Mediated Inhibition of Nrf2 Reverses Hypoxia-Induced 5-Fluorouracil Resistance in Colorectal Cancer.International journal of molecular sciences · 2019Article
- A highly integrated precision nanomedicine strategy to target esophageal squamous cell cancer molecularly and physically.Nanomedicine : nanotechnology, biology, and medicine · 2018Article
- Ipatasertib, a novel Akt inhibitor, induces transcription factor FoxO3a and NF-κB directly regulates PUMA-dependent apoptosis.Cell death & disease · 2018Article
- Anti-survivin effect of the small molecule inhibitor YM155 in RCC cells is mediated by time-dependent inhibition of the NF-κB pathway.Scientific reports · 2018Article
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acquisition of a transformed phenotype involves deregulation of several signal transduction pathways contributing to unconstrained cell growth. Understanding the interplay of different cancer-related signaling pathways is important for development of efficacious multitargeted anticancer drugs. The small molecule 9-aminoacridine (9AA) and its derivative, the antimalaria drug quinacrine, have selective toxicity for tumor cells and can simultaneously suppress nuclear factor-kappaB (NF-kappaB) and activate p53 signaling. To investigate the mechanism underlying these drug activities, we used a combination of two-dimensional protein separation by gel electrophoresis and mass spectrometry to identify proteins whose expression is altered in tumor cells by 9AA treatment. We found that 9AA treatment results in selective downregulation of a specific catalytic subunit of the phosphoinositide 3-kinase (PI3K) family, p110 gamma. Further exploration of this observation demonstrated that the mechanism of action of 9AA involves inhibition of the prosurvival AKT/mammalian target of rapamycin (mTOR) pathway that lies downstream of PI3K. p110 gamma translation appears to be regulated by mTOR and feeds back to further modulate mTOR and AKT, thereby impacting the p53 and NF-kappaB pathways as well. These results reveal functional interplay among the PI3K/AKT/mTOR, p53 and NF-kappaB pathways that are frequently deregulated in cancer and suggest that their simultaneous targeting by a single small molecule such as 9AA could result in efficacious and selective killing of transformed cells.
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