ArticleThe Biochemical journal2012
Interleukin-6 counteracts therapy-induced cellular oxidative stress in multiple myeloma by up-regulating manganese superoxide dismutase.
Article in The Biochemical journal, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 45 citations in OpenAlex.
- A preliminary study of lipid complex supplementation on fatty acid profile and blood antioxidant status after downhill running in athletes.Scientific reports · 2025Trial
- The role of antioxidants in multiple myeloma: diagnostic, prognostic, and therapeutic applications: a narrative review.Therapeutic advances in hematology · 2026Review
- Review
- Pathogenesis of Anemia in Canine Babesiosis: Possible Contribution of Pro-Inflammatory Cytokines and Chemokines-A Review.Pathogens (Basel, Switzerland) · 2023Review
- Targeting prooxidant MnSOD effect inhibits triple-negative breast cancer (TNBC) progression and M2 macrophage functions under the oncogenic stress.Cell death & disease · 2022Article
- Dietary Phytochemicals Targeting Nrf2 to Enhance the Radiosensitivity of Cancer.Oxidative medicine and cellular longevity · 2022Review
- Promoter hypermethylation of early B cell factor 1 (EBF1) is associated with cholangiocarcinoma progression.Journal of Cancer · 2021Article
- Radioprotective Agents and Enhancers Factors. Preventive and Therapeutic Strategies for Oxidative Induced Radiotherapy Damages in Hematological Malignancies.Antioxidants (Basel, Switzerland) · 2020Review
- EPA is Cardioprotective in Male Rats Subjected to Sepsis, but ALA Is Not Beneficial.Antioxidants (Basel, Switzerland) · 2020Article
- Metabolic alterations and the potential for targeting metabolic pathways in the treatment of multiple myeloma.Journal of cancer metastasis and treatment · 2019Article
- A New Natural Antioxidant Mixture Protects against Oxidative and DNA Damage in Endothelial Cell Exposed to Low-Dose Irradiation.Oxidative medicine and cellular longevity · 2017Article
- NADPH Oxidases: Insights into Selected Functions and Mechanisms of Action in Cancer and Stem Cells.Oxidative medicine and cellular longevity · 2017Review
- Metabolic shift toward oxidative phosphorylation in docetaxel resistant prostate cancer cells.Oncotarget · 2016Article
- Role of interleukin-6 in cancer progression and therapeutic resistance.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Review
- Intravenous Iron Carboxymaltose as a Potential Therapeutic in Anemia of Inflammation.PloS one · 2016Article
- Article
- Copper-zinc superoxide dismutase-mediated redox regulation of bortezomib resistance in multiple myeloma.Redox biology · 2015Article
- URI regulates tumorigenicity and chemotherapeutic resistance of multiple myeloma by modulating IL-6 transcription.Cell death & disease · 2014Article
- Scavenger receptor class A member 3 (SCARA3) in disease progression and therapy resistance in multiple myeloma.Leukemia research · 2013Article
- Combination chemotherapy increases cytotoxicity of multiple myeloma cells by modification of nuclear factor (NF)-κB activity.Experimental hematology · 2013Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
IL (interleukin)-6, an established growth factor for multiple myeloma cells, induces myeloma therapy resistance, but the resistance mechanisms remain unclear. The present study determines the role of IL-6 in re-establishing intracellular redox homoeostasis in the context of myeloma therapy. IL-6 treatment increased myeloma cell resistance to agents that induce oxidative stress, including IR (ionizing radiation) and Dex (dexamethasone). Relative to IR alone, myeloma cells treated with IL-6 plus IR demonstrated reduced annexin/propidium iodide staining, caspase 3 activation, PARP [poly(ADP-ribose) polymerase] cleavage and mitochondrial membrane depolarization with increased clonogenic survival. IL-6 combined with IR or Dex increased early intracellular pro-oxidant levels that were causally related to activation of NF-κB (nuclear factor κB) as determined by the ability of N-acetylcysteine to suppress both pro-oxidant levels and NF-κB activation. In myeloma cells, upon combination with hydrogen peroxide treatment, relative to TNF (tumour necrosis factor)-α, IL-6 induced an early perturbation in reduced glutathione level and increased NF-κB-dependent MnSOD (manganese superoxide dismutase) expression. Furthermore, knockdown of MnSOD suppressed the IL-6-induced myeloma cell resistance to radiation. MitoSOX Red staining showed that IL-6 treatment attenuated late mitochondrial oxidant production in irradiated myeloma cells. The present study provides evidence that increases in MnSOD expression mediate IL-6-induced resistance to Dex and radiation in myeloma cells. The results of the present study indicate that inhibition of antioxidant pathways could enhance myeloma cell responses to radiotherapy and/or chemotherapy.
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Registered trials
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