To define the normal physiological role for the TRAIL/Apo2L in vivo, we generated TRAIL/Apo2L gene-targeted mice. These mice develop normally and show no defects in lymphoid or myeloid cell homeostasis or function. Although TRAIL/Apo2L kills transformed cells in vitro, TRAIL/Apo2L(-/-) mice do not spontaneously develop overt tumors at an early age. However, in the A20 B cell lymphoma-transferred tumor model, TRAIL/Apo2L(-/-) mice are clearly more susceptible to death from overwhelming tumor burden, due to increased lymphoma load in the liver. A20 tumors are susceptible to TRAIL/Apo2L killing in vitro, indicating that TRAIL/Apo2L may act directly to control A20 cells in vivo. Despite the fact that TRAIL binds osteoprotegerin and osteoprotegerin-transgenic mice are osteopetrotic, TRAIL/Apo2L(-/-) mice show no evidence of altered gross bone density, and no alterations in frequency or in vitro differentiation of bone marrow precursor osteoclasts. Moreover, leucine zipper TRAIL has no toxicity when repeatedly administered to osteoprotegerin(-/-) mice. Thus, TRAIL/Apo2L is important in controlling tumors in vivo, but is not an essential regulator of osteoprotegerin-mediated biology, under normal physiological conditions.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/1521-4141(200208)32:8<2246::AID-IMMU2246>3.0.CO;2-6 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Colorectal carcinoma cell targeting aromatherapy with Teucrium ramosissimum essential oil to sensitize TRAIL/Apo2L-induced HCT-116 cell death.
Int Immunopharmacol
July 2024
Laboratory of Risks Related to Environmental Stresses: Fight and Prevention, Unit UR03ES06, Faculty of Sciences of Bizerte, University of Carthage, Tunisia.
This report drives insights for the investigation of the underlying mechanisms of antitumor effects of Teucrium ramosissimum (TrS) essential oil (EO) that elicits colon tumor protection via activation of cell death machinery. A study of the aerial part phytocomplex was performed by FTIR spectra and GC/MS. In vivo colon carcinogenesis induced by LPS was carried out using mouse model.
View Article and Find Full Text PDFBoiss. and Reut. volatile oil enhances TRAIL/Apo2L induced apoptosis and inhibits colon carcinogenesis through upregulation of death receptor pathway.
Aging (Albany NY)
September 2021
Laboratory of Biochemistry and Molecular Biology, University of Carthage, Faculty of Sciences of Bizerte, Zarzouna, Bizerte 7021, Tunisia.
Background: The aim of the study is to determine the anticancer activity of (TS) and its underlying mechanisms using and in animal models.
Methods: HCT116 cells were treated with TS essential oil alone or with TRAIL, and then its anticancer effect was determined by using MTT assay, live dead assay, caspase activation and PARP cleavage. Further mechanisms of its anticancer effects was determined by analyzing expression of death receptor signaling pathway using Western blotting.
Oxidative stress-driven DR5 upregulation restores TRAIL/Apo2L sensitivity induced by iron oxide nanoparticles in colorectal cancer.
Biomaterials
March 2020
State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, 361102, China; State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Biology, School of Life Sciences, Xiamen University, Xiamen, 361102, China. Electronic address:
There exists an emergency clinical demand to overcome TRAIL/Apo2L (tumor necrosis factor-related apoptosis-inducing ligand) resistance, which is a major obstacle attributed to insufficient level or mutation of TRAIL receptors. Here, we developed an iron oxide cluster-based nanoplatform for both sensitization and MR image-guided evaluation to improve TRAIL/Apo2L efficacy in colorectal cancer, which has an inadequate response to TRAIL/Apo2L or chemotherapy. Specifically, NanoTRAIL (TRAIL/Apo2L-iron oxide nanoparticles) generated ROS (reactive oxygen species)-triggered JNK (c-Jun N-terminal kinase) activation and induced subsequent autophagy-assisted DR5 upregulation, resulting in a significant enhanced antitumor efficacy of TRAIL/Apo2L, which confirmed in both TRAIL-resistant HT-29, intermediately resistant SW-480 and sensitive HCT-116 cells.
View Article and Find Full Text PDFImproved Anticancer Effect of Recombinant Protein izTRAIL Combined with Sorafenib and Peptide iRGD.
Int J Mol Sci
January 2019
Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, Moscow Region 142290, Russia.
One of the main problems in oncology is the development of drugs that cause the death of cancer cells without damaging normal cells. Another key problem to be solved is to suppress the drug resistance of cancer cells. The third important issue is to provide effective penetration of drug molecules to cancer cells.
View Article and Find Full Text PDFThe Rolipram-Perillyl Alcohol Conjugate (NEO214) Is A Mediator of Cell Death through the Death Receptor Pathway.
Mol Cancer Ther
March 2019
Department of Neurosurgery, Keck School of Medicine, University of Southern California, Los Angeles, California.
Glioblastoma (GBM) is a highly aggressive primary brain tumor with a poor prognosis. Treatment with temozolomide, standard of care for gliomas, usually results in drug resistance and tumor recurrence. Therefore, there is a great need for drugs that target GBM.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!