ArticleBMC cancer2014
Ceramide targets xIAP and cIAP1 to sensitize metastatic colon and breast cancer cells to apoptosis induction to suppress tumor progression.
Article in BMC cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
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Who cites it
28 citing papers in PubMed, 48 citations in OpenAlex.
- Lipidomics reveals the pro-viral roles of ceramides during fish nodavirus infection.Journal of virology · 2026Article
- Egg-derived sphingomyelin induces ferroptosis in cancer cells, depending on intracellular labile iron pool levels.Biochemistry and biophysics reports · 2025Article
- The cross talk of ubiquitination and chemotherapy tolerance in colorectal cancer.Journal of cancer research and clinical oncology · 2024Review
- Therapeutic Potential of Ceramide in Cancer Treatment.Journal of cancer research and oncobiology · 2024Article
- Acid Ceramidase Inhibitor LCL-805 Antagonizes Akt Signaling and Promotes Iron-Dependent Cell Death in Acute Myeloid Leukemia.Cancers · 2023Article
- Upregulation of XIAP promotes lung adenocarcinoma brain metastasis by modulating ceRNA network.Frontiers in oncology · 2022Article
- Endosomes, lysosomes, and the role of endosomal and lysosomal biogenesis in cancer development.Molecular biology reports · 2020Review
- Oridonin enhances the anti-tumor activity of gemcitabine towards pancreatic cancer by stimulating Bax- and Smac-dependent apoptosis.Translational cancer research · 2020Article
- Immunity to X-linked inhibitor of apoptosis protein (XIAP) in malignant melanoma and check-point blockade.Cancer immunology, immunotherapy : CII · 2019Article
- Ceramide Metabolism Balance, a Multifaceted Factor in Critical Steps of Breast Cancer Development.International journal of molecular sciences · 2018Review
- Ceramide species are elevated in human breast cancer and are associated with less aggressiveness.Oncotarget · 2018Article
- Tan IIA inhibits H1299 cell viability through the MDM4‑IAP3 signaling pathway.Molecular medicine reports · 2018Article
- Functional significance and therapeutic implication of ring-type E3 ligases in colorectal cancer.Oncogene · 2018Review
- MicroRNA-509-3p inhibits cell proliferation and invasion via downregulation of X-linked inhibitor of apoptosis in glioma.Oncology letters · 2018Article
- Ceramide activates lysosomal cathepsin B and cathepsin D to attenuate autophagy and induces ER stress to suppress myeloid-derived suppressor cells.Oncotarget · 2016Article
- Ceramide mediates FasL-induced caspase 8 activation in colon carcinoma cells to enhance FasL-induced cytotoxicity by tumor-specific cytotoxic T lymphocytes.Scientific reports · 2016Article
- Piperlongumine induces gastric cancer cell apoptosis and G2/M cell cycle arrest both in vitro and in vivo.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Ceramide-tamoxifen regimen targets bioenergetic elements in acute myelogenous leukemia.Journal of lipid research · 2016Article
- NF-κB functions as a molecular link between tumor cells and Th1/Tc1 T cells in the tumor microenvironment to exert radiation-mediated tumor suppression.Oncotarget · 2016Article
- XIAP inhibitor Embelin inhibits bladder cancer survival and invasion in vitro.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2016Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundCeramide is a bioeffector that mediates various cellular processes, including apoptosis. However, the mechanism underlying ceramide function in apoptosis is apparently cell type-dependent and is not well-understood. We aimed at identifying molecular targets of ceramide in metastatic human colon and breast cancer cells, and determining the efficacy of ceramide analog in suppression of colon and breast cancer metastasis.
methodsThe activity of and mechanism underlying ceramide as a cytotoxic agent, and as a sensitizer for Fas-mediated apoptosis was analyzed in human cell lines established from primary or metastatic colon and breast cancers. The efficacy of ceramide analog LCL85 in suppression of metastasis was examined in preclinical mouse tumor models.
resultsExposure of human colon carcinoma cells to ceramide analog LCL85 results in apoptosis in a dose-dependent manner. Interestingly, a sublethal dose of LCL85 increased C16 ceramide content and overcame tumor cell resistance to Fas-mediated apoptosis. Subsequently, treatment of tumor cells with exogenous C16 ceramide resulted in increased tumor cell sensitivity to Fas-mediated apoptosis. LCL85 resembles Smac mimetic BV6 in sensitization of colon carcinoma cells to Fas-mediated apoptosis by inducing proteasomal degradation of cIAP1 and xIAP proteins. LCL85 also decreased xIAP1 and cIAP1 protein levels and sensitized metastatic human breast cancer cells to Fas-mediated apoptosis. Silencing xIAP and cIAP1 with specific siRNAs significantly increased the metastatic human colon carcinoma cell sensitivity to Fas-mediated apoptosis, suggesting that IAP proteins mediate apoptosis resistance in metastatic human colon carcinoma cells and ceramide induces IAP protein degradation to sensitize the tumor cells to apoptosis induction. Consistent with its apoptosis sensitization activity, subtoxic doses of LCL85 suppressed colon carcinoma cell metastatic potential in an experimental lung metastasis mouse model, as well as breast cancer growth and spontaneous lung metastasis in an orthotopic breast cancer mouse model.
conclusionWe have identified xIAP and cIAP1 as molecular targets of ceramide and determined that ceramide analog LCL85 is an effective sensitizer in overcoming resistance of human cell lines established from metastatic colon and breast cancers to apoptosis induction to suppress metastasis in vivo.
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