ArticleJournal of experimental & clinical cancer research : CR2017
Sulfasalazine attenuates evading anticancer response of CD133-positive hepatocellular carcinoma cells.
Article in Journal of experimental & clinical cancer research : CR, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 69 citations in OpenAlex.
- Synergistic Targeting of Hepatocellular Carcinoma via Novel Regorafenib Combinations with Diosmin, Sulfasalazine, or Rosuvastatin.Biochemical genetics · 2026Article
- Sulfasalazine combined with anti-IL-1β mAb induces ferroptosis and immune modulation in oral squamous cell carcinoma.Cellular and molecular life sciences : CMLS · 2025Article
- Glutathione-associated redox regulation alleviates radio-resistance of canine cancer stem-like cells with low proteasome activity.Scientific reports · 2025Article
- Cellular Membrane Protein GRINA is Highly Expressed and Associated with Survival Outcomes in Liver Cancer Patients.Current medical science · 2025Article
- Comparative analysis of pediatric SHH medulloblastoma DAOY spheres and adherent monolayers: implications for medulloblastoma research.Cancer cell international · 2025Article
- The Cancer Antioxidant Regulation System in Therapeutic Resistance.Antioxidants (Basel, Switzerland) · 2024Review
- Review
- Involvement of Mitochondria in the Selective Response to Microsecond Pulsed Electric Fields on Healthy and Cancer Stem Cells in the Brain.International journal of molecular sciences · 2024Article
- Lipogenesis promotes mitochondrial fusion and maintains cancer stemness in human NSCLC.JCI insight · 2023Article
- Ferroptosis as an emerging therapeutic target in liver diseases.Frontiers in pharmacology · 2023Review
- The current status of tumor microenvironment and cancer stem cells in sorafenib resistance of hepatocellular carcinoma.Frontiers in oncology · 2023Review
- SLC7A11 as a Gateway of Metabolic Perturbation and Ferroptosis Vulnerability in Cancer.Antioxidants (Basel, Switzerland) · 2022Review
- The Role of SLC7A11 in Cancer: Friend or Foe?Cancers · 2022Review
- Correlation between amino acid metabolism and self-renewal of cancer stem cells: Perspectives in cancer therapy.World journal of stem cells · 2022Review
- The Role of Ferroptosis in the Treatment and Drug Resistance of Hepatocellular Carcinoma.Frontiers in cell and developmental biology · 2022Review
- Glutamatergic system components as potential biomarkers and therapeutic targets in cancer in non-neural organs.Frontiers in endocrinology · 2022Review
- Nintedanib Alleviates Experimental Colitis by Inhibiting CEBPB/PCK1 and CEBPB/EFNA1 Pathways.Frontiers in pharmacology · 2022Article
- Antioxidant supplements promote tumor formation and growth and confer drug resistance in hepatocellular carcinoma by reducing intracellular ROS and induction of TMBIM1.Cell & bioscience · 2021Article
- Inhibition of xCT suppresses the efficacy of anti-PD-1/L1 melanoma treatment through exosomal PD-L1-induced macrophage M2 polarization.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- The role of CD133 in hepatocellular carcinoma.Cancer biology & therapy · 2021Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCD133-positive cells in hepatocellular carcinoma (HCC) exhibit cancer stem cell (CSC)-like properties as well as resistance to chemotherapeutic agents and ionizing radiation; however, their function remains unknown. In this paper, we identified a hitherto unknown mechanism to overcome CD133-induced resistance to anticancer therapy.
methodsWe applied an alternative approach to enrich the CD133-positive HCC population by manipulating 3D culture conditions. Defense mechanisms against reactive oxygen species (ROS) in CSC spheroids were evaluated by fluorescence image-based phenotypic screening system. Further, we studied the effect of sulfasalazine on ROS defense system and synergistic therapeutic efficacy of anticancer therapies both in culture and in vivo HCC xenograft mouse model.
resultsHere, we found that oxidative stress increase CD133 expression in HCC and increased CD133 expression enhanced the capacity of the defense system against ROS, and thereby play a central role in resistance to liver cancer therapy. Moreover, ablation of CD133 attenuated not only the capacity for defense against ROS, but also chemoresistance, in HCC through decreasing glutathione (GSH) levels in vitro. Sulfasalazine, a potent xCT inhibitor that plays an important role in maintaining GSH levels, impaired the ROS defense system and increased the therapeutic efficacy of anticancer therapies in CD133-positive HCC but not CD133-negative HCC in vivo and in vitro.
conclusionThese results strongly indicate functional roles for CD133 in ROS defense and in evading anticancer therapies in HCC, and suggest that sulfasalazine, administered in combination with conventional chemotherapy, might be an effective strategy against CD133-positive HCC cells.
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Registered trials
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.