ArticleBritish journal of cancer2008
Chemosensitisation by manganese superoxide dismutase inhibition is caspase-9 dependent and involves extracellular signal-regulated kinase 1/2.
Article in British journal of cancer, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 30 citations in OpenAlex.
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- The Role of Selenium and Manganese in the Formation, Diagnosis and Treatment of Cervical, Endometrial and Ovarian Cancer.International journal of molecular sciences · 2023Review
- Current research progress in the role of reactive oxygen species in esophageal adenocarcinoma.Translational cancer research · 2021Review
- Iron protects childhood acute lymphoblastic leukemia cells from methotrexate cytotoxicity.Cancer medicine · 2020Article
- Valspodar-modulated chemotherapy in human ovarian cancer cells SK-OV-3 and MDAH-2774.Bosnian journal of basic medical sciences · 2019Article
- Exosomes confer chemoresistance to pancreatic cancer cells by promoting ROS detoxification and miR-155-mediated suppression of key gemcitabine-metabolising enzyme, DCK.British journal of cancer · 2017Article
- SOD2 rs4880 CT/CC genotype predicts poor survival for Chinese gastric cancer patients received platinum and fluorouracil based adjuvant chemotherapy.American journal of translational research · 2015Article
- Manganese superoxide dismutase in cancer prevention.Antioxidants & redox signaling · 2014Review
- Article
- Manganese superoxide dismutase promotes anoikis resistance and tumor metastasis.Cell death & disease · 2013Article
- Gecko crude peptides induce apoptosis in human liver carcinoma cells in vitro and exert antitumor activity in a mouse ascites H22 xenograft model.Journal of biomedicine & biotechnology · 2012Article
- Thymosin β10 expression driven by the human TERT promoter induces ovarian cancer-specific apoptosis through ROS production.PloS one · 2012Article
- Hydrogen peroxide: a Jekyll and Hyde signalling molecule.Cell death & disease · 2011Review
- Mechanisms of resistance to photodynamic therapy.Current medicinal chemistry · 2011Review
- Computational identification and experimental validation of PPRE motifs in NHE1 and MnSOD genes of human.BMC genomics · 2009Article
- Characterization of intracellular superoxide dismutase alterations in premalignant and malignant lesions of the oral cavity: correlation with lymph node metastasis.Journal of cancer research and clinical oncology · 2009Article
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7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chemoresistance and therapeutic selectivity are major obstacles to successful chemotherapy of ovarian cancer. Manganese superoxide disumutase (MnSOD) is an important antioxidant enzyme responsible for the elimination of superoxide radicals. We reported here that MnSOD was significantly elevated in ovarian cancer cells and its overexpression was one of the mechanisms that increased resistance to apoptosis in cancer cells. Knockdown of MnSOD by small-interfering RNA (siRNA) led to an increase in superoxide generation and sensitisation of ovarian cancer cells to the two front-line anti-cancer agents doxorubicin and paclitaxel whose action involved free-radical generation. This synergistic effect was not observed in non-transformed ovarian surface epithelial cells. Furthermore, our results revealed that this combination at the cellular level augmented activation of caspase-3 and caspase-9, but not caspase-8, suggesting involvement of an intrinsic apoptotic pathway. Evaluation of signalling pathways showed that MnSOD siRNA enhanced doxorubicin- and paclitaxel-induced phosphorylation of extracellular signal-regulated kinase 1/2. Akt activation was not affected. These results identify a novel chemoresistance mechanism in ovarian cancer, and show that combination of drugs capable of suppressing MnSOD with conventional chemotherapeutic agents may provide a novel strategy with a superior therapeutic index and advantage for the treatment of refractory ovarian cancer.
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