ArticleProceedings of the National Academy of Sciences of the United States of America2009
A systems biology understanding of the synergistic effects of arsenic sulfide and Imatinib in BCR/ABL-associated leukemia.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 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
50 citing papers in PubMed, 122 citations in OpenAlex.
- Oral arsenic plus imatinib versus imatinib solely for newly diagnosed chronic myeloid leukemia: a randomized phase 3 trial with 5-year outcomes.Journal of cancer research and clinical oncology · 2024Trial
- Effects of realgar-indigo naturalis formula on a zebrafish tumor xenograft model induced by human acute promyelocytic leukemia cells: antitumor activity, hepatotoxicity, and transcriptomic analysis.Frontiers in pharmacology · 2025Article
- Blockage of Autophagy for Cancer Therapy: A Comprehensive Review.International journal of molecular sciences · 2024Review
- Article
- ER Stress and Unfolded Protein Response in Leukemia: Friend, Foe, or Both?Biomolecules · 2021Review
- Antitumor effects of arsenic disulfide on the viability, migratory ability, apoptosis and autophagy of breast cancer cells.Oncology reports · 2019Article
- Regulatory Molecules and Corresponding Processes of BCR-ABL Protein Degradation.Journal of Cancer · 2019Review
- Arsenic circumvents the gefitinib resistance by binding to P62 and mediating autophagic degradation of EGFR in non-small cell lung cancer.Cell death & disease · 2018Article
- Anticancer efficacies of arsenic disulfide through apoptosis induction, cell cycle arrest, and pro-survival signal inhibition in human breast cancer cells.American journal of cancer research · 2018Article
- Development of Fangjiomics for Systems Elucidation of Synergistic Mechanism Underlying Combination Therapy.Computational and structural biotechnology journal · 2018Review
- Poly (ADP-Ribose) Polymerase 1 Mediated Arginase II Activation Is Responsible for Oxidized LDL-Induced Endothelial Dysfunction.Frontiers in pharmacology · 2018Article
- Realgar nanoparticles versus ATO arsenic compounds induce in vitro and in vivo activity against multiple myeloma.British journal of haematology · 2017Article
- Time-series analysis in imatinib-resistant chronic myeloid leukemia K562-cells under different drug treatments.Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban · 2017Article
- Accumulation of Arsenic Speciation andFrontiers in pharmacology · 2017Article
- The chimeric ubiquitin ligase SH2-U-box inhibits the growth of imatinib-sensitive and resistant CML by targeting the native and T315I-mutant BCR-ABL.Scientific reports · 2016Article
- Role of Oxidative Stress in Modulating Unfolded Protein Response Activity in Chronic Myeloid Leukemia Cell Line.Iranian biomedical journal · 2016Article
- Traditional Chinese medicine and cancer: History, present situation, and development.Thoracic cancer · 2015Review
- Realgar quantum dots induce apoptosis and necrosis in HepG2 cells through endoplasmic reticulum stress.Biomedical reports · 2015Article
- Arsenic sulfide as a potential anti‑cancer drug.Molecular medicine reports · 2015Article
- Exploring the ligand-protein networks in traditional chinese medicine: current databases, methods and applications.Advances in experimental medicine and biology · 2015Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In this study, we show that combined use of Imatinib (IM) and arsenic sulfide [As(4)S(4) (AS)] exerts more profound therapeutic effects in a BCR/ABL-positive mouse model of chronic myeloid leukemia (CML) than either drug as a single agent. A systematic analysis of dynamic changes of the proteome, phosphoproteome, and transcriptome in K562 cells after AS and/or IM treatment was performed to address the mechanisms underlying this synergy. Our data indicate that AS promotes the activities of the unfolded protein reaction (UPR) and ubiquitination pathway, which could form the biochemical basis for the pharmacological effects of this compound. In this CML model, AS targets BCR/ABL through the ubiquitination of key lysine residues, leading to its proteasomal degradation, whereas IM inhibits the PI3K/AKT/mTOR pathway. Combination of the 2 agents synergistically arrests the cell cycle, decreases activity of BCR/ABL, and leads to activation of intrinsic and extrinsic apoptosis pathways through complex modifications to both transcription and protein levels. Thus, these results suggest potential clinical benefits of IM/AS combination therapy for human CML.
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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.