The availability of TRAIL receptor agonist antibodies or TRAIL pathway stimulating/activating small molecules such as ONC201 in multiple clinical trials points towards the future. The results of the analyses were published in Cancer Letters. Several strategies appear as particularly promising, including new TRAIL receptor agonists, Smac and BH3 mimetics, as well as selective kinase inhibitors. The tumor-promoting effects of these interactions become particularly important for consideration in cases where tumors are resistant to TRAIL-induced apoptosis. Through investigation of mitochondria membrane potential, we found that MSC-TRAIL was capable of inducing intrinsic apoptosis to the CSCs. TRAIL binds to five different receptors. AML comprises a heterogeneous group of malignancies, characterized by a combination of different somatic genetic abnormalities, some of which act as events driving leukemic development. To address this issue, combination strategies were tested, and survival pathway inhibitors were shown to sensitize melanoma cells for TRAIL-induced apoptosis. Once you are registered, click here to go to the submission form. Cell therapy is a promising new treatment option for cancer. �|Yfi?�O%�:��8��o�%ncL�Q�ɭ���ߋcť4EK���G���ɗ'GТ^L�]�Ci�i*]�n. By continuing you agree to the use of cookies. Copyright © 2020 Elsevier B.V. or its licensors or contributors.
Apoptosis was detected by flow cytometry with annexin V-FITC/propidium iodide and by fluorescence microscopy with Hoechst 33342/annexin V-FITC/Ethidium Homodimer. Inducible TRAIL resistance in melanoma can be explained by (i) high levels of antiapoptotic Bcl-2 proteins, (ii) high levels of XIAP, and (iii) suppressed Bax activity.
It is therefore important to overcome this resistance for the clinical use of TRAIL in cancer therapy. Three human bladder transitional cancer cell (TCC) lines - SW780, 647V and T24 were tested for TRAIL sensitivity. TRAIL receptor signaling and therapeutics. You seem to have javascript disabled. National Center for Biotechnology Information, Unable to load your collection due to an error, Unable to load your delegates due to an error. In this regard, cells involved in tumor immunosurveillance, such as activated human T cells, secrete endogenous TRAIL as a transmembrane protein associated with lipid microvesicles called exosomes upon T-cell reactivation. We have now tested agonistic receptor-specific TRAIL variants rhTRAIL 4C7 and DHER in combination with several class I specific HDACi’s on TRAIL-resistant colon cancer cells DLD-1 and WiDr. Members of the tumor … Using assays to evaluate cell proliferation, apoptosis, and gene expression, Mesenchymal stem cells (MSCs) are emerging as vehicles for anti-tumor cytotherapy; however, investigation on its efficacy to target a specific cancer stem cell (CSC) population in non-small cell lung cancer (NSCLC) is lacking. Notably, DR5 was translocated to the autophagosomes and underwent a lysosomal degradation.
This discovery led to evaluation of TRAIL-R1/-R2 as targets for anti-cancer therapy, yet the corresponding clinical trials were disappointing. Bufalin sensitizes human bladder carcinoma cells to TRAIL-mediated apoptosis.
TRAIL death receptors are attractive therapeutic targets in cancer treatment. Both membrane-expressed TRAIL and soluble TRAIL can induce apoptosis in a wide variety of tumor cell lines, whereas normal cells are relatively resistant. WP1130-induced c-FLIP downregulation was regulated by microRNA (miR)-708 upregulation via inhibition of USP9X. Expression of TRAIL (tumor necrosis factor–related apoptosis–inducing ligand) by immune cells can lead to the induction of apoptosis in tumor cells. © 2020 MJH Life Sciences™ and . The naturally occurring gld (generalized lymphoproliferative disease) and lpr (lymphoproliferation) mutant mice … However, euphoria gave way to disillusionment as it turned out that carcinoma cells possess or can acquire resistance to TRAIL-induced apoptosis. TRAIL binds to the death receptors DR4 (TRAIL-RI) and DR5 (TRAIL-RII). Our dedicated information section provides allows you to learn more about MDPI. As nuclear trafficking of TRAIL-Rs is not well understood, we addressed this issue in our present study. Melanoma of the skin has become a prime example for demonstrating the success of targeted cancer therapy. Nat. One of the main characteristics of carcinogenesis relies on genetic alterations in DNA and epigenetic changes in histone and non-histone proteins. Circulating tumor cells (CTCs) in the peripheral blood are the precursors to distant metastasis but the underlying mechanisms are poorly understood.