ArticleCancer cell international2024
The sensitivity of acute myeloid leukemia cells to cytarabine is increased by suppressing the expression of Heme oxygenase-1 and hypoxia-inducible factor 1-alpha.
Article in Cancer cell international, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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11 citing papers in PubMed.
- IL-6/IL-6R-Mediated Mechanisms in Lung Cancer: From Pathogenesis to Potential Therapeutic Targets.Immunology · 2026Review
- Oncostatin M as a Multifunctional Regulator of Breast Cancer Progression: Current Insights and Future Therapeutic Avenues.IUBMB life · 2026Review
- HO-1-driven drug resistance in hematological malignancies: Mechanistic insights and advances in targeted therapy.iScience · 2026Review
- Vitexin Attenuates the Growth and Glycolysis of Acute Myeloid Leukemia Cells by Suppressing the HIF-1α-Modulated YAP Pathway Under Hypoxic Conditions.The Kaohsiung journal of medical sciences · 2026Article
- Clinico-genomic characterization of RAS-mutant acute myeloid leukemia.Annals of hematology · 2026Article
- The role of hypoxia-inducible factor-1α on colon cancer progression and metastasis.International journal of clinical oncology · 2025Review
- Therapeutic innovations: targeting ROS production in AML with natural and synthetic compounds.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Endoplasmic Reticulum Stress in Acute Myeloid Leukemia: Pathogenesis, Prognostic Implications, and Therapeutic Strategies.International journal of molecular sciences · 2025Review
- Targeting the hypoxia signaling pathway with nanomedicine to reverse immunotherapy resistance.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Ferroptosis: Potential therapeutic targets and prognostic predictions for acute myeloid leukemia (Review).Oncology letters · 2024Review
- Survival impact of hypoxia-inducible factor-1 alpha (HIF-1α) in Nucleophosmin1 mutated acute myeloid leukemia.Annals of hematology · 2024Article
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Abstract
backgroundAcute myeloid leukemia (AML), a malignancy Often resistant to common chemotherapy regimens (Cytarabine (Ara-c) + Daunorubicin (DNR)), is accompanied by frequent relapses. Many factors are involved in causing chemoresistance. Heme Oxygenase-1 (HO-1) and Hypoxia-Inducible Factor 1-alpha (HIF-1α) are two of the most well-known genes, reported to be overexpressed in AML and promote resistance against chemotherapy according to several studies. The main chemotherapy agent used for AML treatment is Ara-c. We hypothesized that simultaneous targeting of HO-1 and HIF-1α could sensitize AML cells to Ara-c.
methodIn this study, we used our recently developed, Trans-Activator of Transcription (TAT) - Chitosan-Carboxymethyl Dextran (CCMD) - Poly Ethylene Glycol (PEG) - Nanoparticles (NPs), to deliver Ara-c along with siRNA molecules against the HO-1 and HIF-1α genes to AML primary cells (ex vivo) and cell lines including THP-1, KG-1, and HL-60 (in vitro). Subsequently, the effect of the single or combinational treatment on the growth, proliferation, apoptosis, and Reactive Oxygen Species (ROS) formation was evaluated.
resultsThe designed NPs had a high potential in transfecting cells with siRNAs and drug. The results demonstrated that treatment of cells with Ara-c elevated the generation of ROS in the cells while decreasing the proliferation potential. Following the silencing of HO-1, the rate of apoptosis and ROS generation in response to Ara-c increased significantly. While proliferation and growth inhibition were considerably evident in HIF-1α-siRNA-transfected-AML cells compared to cells treated with free Ara-c. We found that the co-inhibition of genes could further sensitize AML cells to Ara-c treatment.
conclusionsAs far as we are aware, this study is the first to simultaneously inhibit the HO-1 and HIF-1α genes in AML using NPs. It can be concluded that HO-1 causes chemoresistance by protecting cells from ROS damage. Whereas, HIF-1α mostly exerts prolific and direct anti-apoptotic effects. These findings imply that simultaneous inhibition of HO-1 and HIF-1α can overcome Ara-c resistance and help improve the prognosis of AML patients.
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