ArticleClinical cancer research : an official journal of the American Association for Cancer Research2008
Molecularly targeted radiosensitization of human prostate cancer by modulating inhibitor of apoptosis.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 59 citations in OpenAlex.
- cIAP1/2 are involved in the radiosensitizing effect of birinapant on NSCLC cell line in vitro.Journal of cellular and molecular medicine · 2021Article
- Understanding Apoptosis and Apoptotic Pathways Targeted Cancer Therapeutics.Advanced pharmaceutical bulletin · 2019Review
- Biological determinants of radioresistance and their remediation in pancreatic cancer.Biochimica et biophysica acta. Reviews on cancer · 2017Review
- Overcoming chemo/radio-resistance of pancreatic cancer by inhibiting STAT3 signaling.Oncotarget · 2016Article
- PTEN deficiency promotes macrophage infiltration and hypersensitivity of prostate cancer to IAP antagonist/radiation combination therapy.Oncotarget · 2016Article
- Potential of apoptotic pathway-targeted cancer therapeutic research: Where do we stand?Cell death & disease · 2016Review
- XRCC2 as a predictive biomarker for radioresistance in locally advanced rectal cancer patients undergoing preoperative radiotherapy.Oncotarget · 2015Article
- Targeting IAP proteins in combination with radiotherapy.Radiation oncology (London, England) · 2015Review
- The retinoblastoma tumor suppressor modulates DNA repair and radioresponsiveness.Clinical cancer research : an official journal of the American Association for Cancer Research · 2014Article
- The BIRC6 gene as a novel target for therapy of prostate cancer: dual targeting of inhibitors of apoptosis.Oncotarget · 2014Article
- Antibody against CD44s inhibits pancreatic tumor initiation and postradiation recurrence in mice.Gastroenterology · 2014Article
- ATDC/TRIM29 phosphorylation by ATM/MAPKAP kinase 2 mediates radioresistance in pancreatic cancer cells.Cancer research · 2014Article
- Smac mimetic compound LCL161 sensitizes esophageal carcinoma cells to radiotherapy by inhibiting the expression of inhibitor of apoptosis protein.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014Article
- Embelin, a small molecule quinone with a co-clinical power for castrate-resistant prostate cancer.Frontiers in pharmacology · 2014Article
- Targeting the alternative NF-κB pathway in pancreatic cancer: a new direction for therapy?Expert review of anticancer therapy · 2013Article
- Targeting IAP proteins for therapeutic intervention in cancer.Nature reviews. Drug discovery · 2012Review
- BV6, an IAP antagonist, activates apoptosis and enhances radiosensitization of non-small cell lung carcinoma in vitro.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2011Article
- Radiosensitization of human breast cancer cells to ultraviolet light by 5-fluorouracil.Oncology letters · 2011Article
- Natural IAP inhibitor Embelin enhances therapeutic efficacy of ionizing radiation in prostate cancer.American journal of cancer research · 2011Article
- Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
purposeThe inhibitor of apoptosis proteins (IAP) are overexpressed in hormone-refractory prostate cancer, rendering the cancer cells resistant to radiation. This study aims to investigate the radiosensitizing effect of small-molecule IAP inhibitor both in vitro and in vivo in androgen-independent prostate cancer and the possible mechanism of radiosensitization. EXPERIMENTAL
designRadiosensitization of SH-130 in human prostate cancer DU-145 cells was determined by clonogenic survival assay. Combination effect of SH-130 and ionizing radiation was evaluated by apoptosis assays. Pull-down and immunoprecipitation assays were employed to investigate the interaction between SH-130 and IAPs. DU-145 xenografts in nude mice were treated with SH-130, radiation, or combination, and tumor suppression effect was determined by caliper measurement or bioluminescence imaging. Nuclear factor-kappaB activation was detected by luciferase reporter assay and quantitative real-time PCR.
resultsSH-130 potently enhanced radiation-induced caspase activation and apoptosis in DU-145 cells. Both X-linked IAP and cIAP-1 can be pulled down by SH-130 but not by inactive SH-123. Moreover, SH-130 interrupted interaction between X-linked IAP/cIAP-1 and Smac. In a nude mouse xenograft model, SH-130 potently sensitized the DU-145 tumors to X-ray radiation without increasing systemic toxicity. The combination therapy suppressed tumor growth more significantly than either treatment alone, with over 80% of complete tumor regression. Furthermore, SH-130 partially blocked tumor necrosis factor-alpha- and radiation-induced nuclear factor-kappaB activation in DU-145 cells.
conclusionsOur results show that small-molecule inhibitors of IAPs can overcome apoptosis resistance and radiosensitize human prostate cancer with high levels of IAPs. Molecular modulation of IAPs may improve the outcome of prostate cancer radiotherapy.
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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.