ArticleCancer chemotherapy and pharmacology2010
Se-methylselenocysteine sensitizes hypoxic tumor cells to irinotecan by targeting hypoxia-inducible factor 1alpha.
Article in Cancer chemotherapy and pharmacology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 67 citations in OpenAlex.
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- Selenium compounds for cancer prevention and therapy - human clinical trial considerations.Medical review (2021) · 2025Review
- Associations between HIFs and tumor immune checkpoints: mechanism and therapy.Discover oncology · 2024Review
- Selenium in cancer management: exploring the therapeutic potential.Frontiers in oncology · 2024Review
- Druggable Biomarkers Altered in Clear Cell Renal Cell Carcinoma: Strategy for the Development of Mechanism-Based Combination Therapy.International journal of molecular sciences · 2023Review
- Potential Role of Selenium in the Treatment of Cancer and Viral Infections.International journal of molecular sciences · 2022Review
- THE MAIN CYTOTOXIC EFFECTS OF METHYLSELENINIC ACID ON VARIOUS CANCER CELLS.International journal of molecular sciences · 2021Review
- Utilization of redox modulating small molecules that selectively act as pro-oxidants in cancer cells to open a therapeutic window for improving cancer therapy.Redox biology · 2021Review
- Escape From Cisplatin-Induced Senescence of Hypoxic Lung Cancer Cells Can Be Overcome by Hydroxychloroquine.Frontiers in oncology · 2021Article
- Understanding the Redox Biology of Selenium in the Search of Targeted Cancer Therapies.Antioxidants (Basel, Switzerland) · 2020Review
- Dissecting the Proton Transport Pathway in Oral Squamous Cell Carcinoma: State of the Art and Theranostics Implications.International journal of molecular sciences · 2019Review
- Methylseleninic Acid Induces Lipid Peroxidation and Radiation Sensitivity in Head and Neck Cancer Cells.International journal of molecular sciences · 2019Article
- Selenium Species: Current Status and Potentials in Cancer Prevention and Therapy.International journal of molecular sciences · 2018Review
- Non-Coding Micro RNAs and Hypoxia-Inducible Factors Are Selenium Targets for Development of a Mechanism-Based Combination Strategy in Clear-Cell Renal Cell Carcinoma-Bench-to-Bedside Therapy.International journal of molecular sciences · 2018Article
- The role of hypoxic signalling in metastasis: towards translating knowledge of basic biology into novel anti-tumour strategies.Clinical & experimental metastasis · 2018Review
- Selenium targets resistance biomarkers enhancing efficacy while reducing toxicity of anti-cancer drugs: preclinical and clinical development.Oncotarget · 2018Review
- Oxidative stress mediates an increased formation of vascular endothelial growth factor in human hepatocarcinoma cells exposed to erlotinib.Oncotarget · 2017Article
- The CDK4/6 inhibitor palbociclib synergizes with irinotecan to promote colorectal cancer cell death under hypoxia.Cell cycle (Georgetown, Tex.) · 2017Article
- GC7 blocks epithelial-mesenchymal transition and reverses hypoxia-induced chemotherapy resistance in hepatocellular carcinoma cells.American journal of translational research · 2017Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
purposeHypoxic tumor cells overexpressing hypoxia-inducible factor 1alpha (HIF-1alpha) are generally resistant to chemo/radiotherapy. We have reported that Se-methylselenocysteine (MSC) therapeutically enhances the efficacy and selectivity of irinotecan against human tumor xenografts. The aim of this study was to delineate the mechanism responsible for the observed efficacy targeting on HIF-1alpha and its transcriptionally regulated genes VEGF and CAIX.
methodsWe investigated the mechanism of HIF-1alpha inhibition by MSC and its critical role in the therapeutic outcome by generating HIF-1alpha stable knockdown (KD) human head and neck squamous cell carcinoma, FaDu by transfecting HIF-1alpha short hairpin RNA.
resultsWhile cytotoxic efficacy in combination with methylselenic acid (MSA) with SN-38 (active metabolites of MSC and irinotecan) could not be confirmed in vitro against normoxic tumor cells, the hypoxic tumor cells were more sensitive to the combination. Reduction in HIF-1alpha either by MSA or shRNA knockdown resulted in significant increase in cytotoxicity of SN38 in vitro against hypoxic, but not the normoxic tumor cells. Similarly, in vivo, either MSC in combination with irinotecan treatment of parental xenografts or HIF-1alpha KD tumors treated with irinotecan alone resulted in comparable therapeutic response and increase in the long-term survival of mice bearing FaDu xenografts.
conclusionsOur results show that HIF-1alpha is a critical target for MSC and its inhibition was associated with enhanced antitumor activity of irinotecan. Inhibition of HIF-1alpha appeared to be mediated through stabilization of PHD2, 3 and downregulation of ROS by MSC. Thus, our findings support the development of MSC as a HIF-1alpha inhibitor in combination chemotherapy.
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