Carboplatin induces Fas (APO‐1/CD95)‐dependent apoptosis of human tongue carcinoma cells: Sensitization for apoptosis by upregulation of FADD expression
- 25 March 2003
- journal article
- research article
- Published by Wiley in International Journal of Cancer
- Vol. 105 (5) , 593-600
- https://doi.org/10.1002/ijc.11133
Abstract
We examined the apoptosis of tongue carcinoma cells and the effects of anticancer drugs to identify the molecules that mediate apoptotic cascade in the malignancy. Carboplatin (CBDCA) induced apoptosis of SCC‐9 and SCC‐25, human well‐differentiated tongue squamous carcinoma cell lines. Neutralizing anti‐Fas (APO‐1/CD95) and anti‐Fas ligand (FasL) antibodies obliterated the CBDCA‐induced cell death. In the absence of CBDCA, cytotoxic anti‐Fas antibody, which binds to and activates Fas at the cell surface, failed to induce apoptosis. However, in the presence of CBDCA, the cytotoxic antibody markedly enhanced the apoptosis in a dose‐dependent manner. Western blotting and reverse‐transcription (RT) PCR revealed that there were no alterations in Fas or FasL expression upon CBDCA treatment. SCC‐25 induced apoptosis of Jurkat cells, Fas‐sensitive T‐lymphatic leukemia cell line, and the apoptosis was inhibited by neutralizing anti‐Fas or anti‐FasL antibody. These results indicate that the tongue carcinoma cells express nonfunctional Fas and functional FasL, which by themselves fail to induce apoptosis. The expression of FADD in the tongue carcinoma cells was very low and was largely enhanced by CBDCA treatment. Suppression of FADD expression using the specific antisense oligonucleotide resulted in a failure of CBDCA induction of cell death. These results indicate that a deficiency of FADD is involved in the insensitivity of tongue carcinoma cells for Fas activation, and that CBDCA treatment switches nonfunctional Fas to functional Fas by upregulation of FADD expression, resulting in activation of a Fas‐sensitive pathway leading to apoptosis.Keywords
This publication has 37 references indexed in Scilit:
- Apoptosis in the development of the temporomandibular jointBrain Structure and Function, 1997
- Molecular ordering of the Fas-apoptotic pathway: The Fas/APO-1 protease Mch5 is a CrmA-inhibitable protease that activates multiple Ced-3/ICE-like cysteine proteasesProceedings of the National Academy of Sciences, 1996
- FLICE, A Novel FADD-Homologous ICE/CED-3–like Protease, Is Recruited to the CD95 (Fas/APO-1) Death-Inducing Signaling ComplexCell, 1996
- The molecular biology of apoptosis.Proceedings of the National Academy of Sciences, 1996
- FADD, a novel death domain-containing protein, interacts with the death domain of fas and initiates apoptosisCell, 1995
- Apoptosis in the Pathogenesis and Treatment of DiseaseScience, 1995
- Molecular cloning and expression of the fas ligand, a novel member of the tumor necrosis factor familyCell, 1993
- Mechanisms and Functions of Cell DeathAnnual Review of Cell Biology, 1991
- The polypeptide encoded by the cDNA for human cell surface antigen Fas can mediate apoptosisCell, 1991
- Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activationNature, 1980