ArticleBritish journal of cancer2009
MLH1 expression sensitises ovarian cancer cells to cell death mediated by XIAP inhibition.
Article in British journal of cancer, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 28 citations in OpenAlex.
- Platinum chemotherapeutic-induced oxidative stress affects the transcriptional response of DNA repair genes in murine mesenchymal stem cells.American journal of stem cells · 2025Article
- miR-874-3p mitigates cisplatin resistance through modulating NF-κB/inhibitor of apoptosis protein signaling pathway in epithelial ovarian cancer cells.Molecular and cellular biochemistry · 2022Article
- High temperature requirement A1 in cancer: biomarker and therapeutic target.Cancer cell international · 2021Review
- A Preliminary Study of NER and MMR Pathways Involved in Chemotherapy Response in Bladder Transitional Cell Carcinoma: Impact on progression-free survival.Iranian journal of pharmaceutical research : IJPR · 2020Article
- Synthesis of novel 10,11-methylenedioxy-camptothecin glycoside derivatives and investigation of their anti-tumor effectsRSC advances · 2019Article
- A Whole-genome CRISPR Screen Identifies a Role of MSH2 in Cisplatin-mediated Cell Death in Muscle-invasive Bladder Cancer.European urology · 2019Article
- MLH1 enhances the sensitivity of human endometrial carcinoma cells to cisplatin by activating the MLH1/c-Abl apoptosis signaling pathway.BMC cancer · 2018Article
- Prognostic values of DNA mismatch repair genes in ovarian cancer patients treated with platinum-based chemotherapy.Archives of gynecology and obstetrics · 2018Article
- Article
- MLH1 as a direct target of MiR-155 and a potential predictor of favorable prognosis in pancreatic cancer.Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract · 2013Article
- HtrA1 sensitizes ovarian cancer cells to cisplatin-induced cytotoxicity by targeting XIAP for degradation.International journal of cancer · 2012Article
- Sodium arsenite and hyperthermia modulate cisplatin-DNA damage responses and enhance platinum accumulation in murine metastatic ovarian cancer xenograft after hyperthermic intraperitoneal chemotherapy (HIPEC).Journal of ovarian research · 2011Article
- Cellular responses to Cisplatin-induced DNA damage.Journal of nucleic acids · 2010Article
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundThe X-linked inhibitor of apoptosis protein (XIAP), an endogenous apoptosis suppressor, can determine the level of caspase accumulation and the resultant response to apoptosis-inducing agents such as cisplatin in epithelial ovarian cancer (EOC). In addition, the mismatch repair protein, hMLH1, has been linked to DNA damage-induced apoptosis by cisplatin by both p53-dependent and -independent mechanisms.
methodsIn this study, hMLH1 expression was correlated with clinical response to platinum drugs and survival in advanced stage (III-IV) EOC patients. We then investigated whether MLH1 loss was a determinant in anti-apoptosis response to cisplatin mediated by XIAP in isogenic and established EOC cell lines with differential p53 status.
resultsThe percentage of cells undergoing cisplatin-induced cell killing was higher in MLH1-proficient cells than in MLH1-defective cells. In addition, the presence of wild-type hMLH1 or hMLH1 re-expression significantly increased sensitivity to 6-thioguanine, a MMR-dependent agent. Cell-death response to 6-thioguanine and cisplatin was associated with significant proteolysis of MLH1, with XIAP destabilisation and increased caspase-3 activity. The siRNA-mediated inhibition of XIAP increased MLH1 proteolysis and cell death in MLH1-proficient cells but not in MLH1-defective cells.
conclusionThese data suggest that XIAP inhibitors may prove to be an effective means of sensitising EOC to MLH1-dependent apoptosis.
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