ArticleBritish journal of cancer2008
Double inhibition of XIAP and Bcl-2 axis is beneficial for retrieving sensitivity of renal cell cancer to apoptosis.
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 20 papers.
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Who cites it
20 citing papers in PubMed, 49 citations in OpenAlex.
- Development of patient‑derived tumor organoids and a drug testing model for renal cell carcinoma.Oncology reports · 2021Article
- Kidney cancer biomarkers and targets for therapeutics: survivin (BIRC5), XIAP, MCL-1, HIF1α, HIF2α, NRF2, MDM2, MDM4, p53, KRAS and AKT in renal cell carcinoma.Journal of experimental & clinical cancer research : CR · 2021Review
- The SMAC mimetic AT-101 exhibits anti-tumor and anti-metastasis activity in lung adenocarcinoma cells by the IAPs/ caspase-dependent apoptosis and p65-NFƙB cross-talk.Iranian journal of basic medical sciences · 2021Article
- Histone deacetylase 6 inhibition in urothelial cancer as a potential new strategy for cancer treatment.Oncology letters · 2021Article
- A small-molecule ARTS mimetic promotes apoptosis through degradation of both XIAP and Bcl-2.Cell death & disease · 2020Article
- Isobaric tags for relative and absolute quantitation-based quantitative proteomic analysis of X-linked inhibitor of apoptosis and H2AX in etoposide-induced renal cell carcinoma apoptosis.Chinese medical journal · 2019Article
- XIAP impairs mitochondrial function during apoptosis by regulating the Bcl-2 family in renal cell carcinoma.Experimental and therapeutic medicine · 2018Article
- Article
- XIAP underlies apoptosis resistance of renal cell carcinoma cells.Molecular medicine reports · 2018Article
- Potential biological process of X-linked inhibitor of apoptosis protein in renal cell carcinoma based upon differential protein expression analysis.Oncology letters · 2018Article
- Decreased Expression of SRSF2 Splicing Factor Inhibits Apoptotic Pathways in Renal Cancer.International journal of molecular sciences · 2016Article
- Uncoupling of PUMA Expression and Apoptosis Contributes to Functional Heterogeneity in Renal Cell Carcinoma - Prognostic and Translational Implications.Translational oncology · 2015Article
- Harnessing the p53-PUMA axis to overcome DNA damage resistance in renal cell carcinoma.Neoplasia (New York, N.Y.) · 2014Article
- Tissue microarray analysis of X-linked inhibitor of apoptosis (XIAP) expression in breast cancer patients.Medical oncology (Northwood, London, England) · 2014Article
- PI3K inhibition potentiates Bcl-2-dependent apoptosis in renal carcinoma cells.Journal of cellular and molecular medicine · 2013Article
- Bcl-2 family of proteins as therapeutic targets in genitourinary neoplasms.Clinical genitourinary cancer · 2013Review
- Novel second mitochondria-derived activator of caspases (Smac) mimetic compounds sensitize human leukemic cell lines to conventional chemotherapeutic drug-induced and death receptor-mediated apoptosis.Investigational new drugs · 2011Article
- Control of cell survival and proliferation by mammalian eukaryotic initiation factor 4B.Molecular and cellular biology · 2010Article
- Glycogen synthase kinase-3: a new therapeutic target in renal cell carcinoma.British journal of cancer · 2009Article
- Down-regulation of cIAP2 enhances 5-FU sensitivity through the apoptotic pathway in human colon cancer cells.Cancer science · 2009Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Renal cell carcinoma (RCC) is known to be resistant to chemo- and radiotherapy due to a high apoptotic threshold. Smac and XIAP (X-linked inhibitor of apoptosis protein) proteins were detected in all RCC cell lines and tissue samples examined. We modulated the function of XIAP, either through its constitutional downregulation with an shRNA vector or by applying a Smac-mimicking peptide. Among RCC cell lines, Caki1 expresses the highest levels of XIAP. We transfected Caki1 with XIAP-targeting shRNA vector and generated stable clones. XIAP was knocked down by RNA interference in clone no. 14 by 81.6% and in clone no. 19 by 85.3%. Compared to the parental and mock-transfected cells, neither clone was more sensitive to conventional chemotherapeutic agents, but both clones were more susceptible to Fas stimulation (P<0.0001) and to pharmacological Bcl-2 inhibition (P<0.0001), as well as to a combination of the two (P<0.0001). Mature Smac binds to XIAP via the N-terminal residues, disrupting its interaction with caspases and promoting their activity. We determined that exposure of Caki1 cells to Smac-N7 peptide (AVPIAQK) resulted in a slight but significant decrease in viability (P=0.0031) and potentiated cisplatin's effect (P=0.0027). In contrast with point targeting of XIAP by shRNA, Smac-N7 peptide is active against several IAP (inhibitor of apoptosis protein) family members, which can explain its role in sensitising cells to cisplatin. Our results suggest that multiple targeting of both Bcl-2 and XIAP or, alternatively, of several IAP family members by the Smac-N7 peptide is a potent way to overcome resistance of RCC to apoptosis-triggering treatment modalities, and might be a new tool for molecular targeted therapy.
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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.