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Drug‐induced apoptosis in osteosarcoma cell lines is mediated by caspase activation independent of CD95‐receptor/ligand interaction
Author(s) -
Fellenberg J.,
Mau H.,
Nedel S.,
Ewerbeck V.,
Debatin KM.
Publication year - 2000
Publication title -
journal of orthopaedic research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1002/jor.1100180103
Subject(s) - fas receptor , apoptosis , osteosarcoma , fas ligand , cytotoxic t cell , cancer research , caspase , receptor , caspase 8 , intrinsic apoptosis , programmed cell death , microbiology and biotechnology , biology , chemistry , biochemistry , in vitro
Osteosarcoma is one of the most common primary malignant tumors of bone. Treatment of this tumor with systemic chemotherapy dramatically improves the prognosis, although the molecular mechanisms involved in the drug action are poorly understood. In chemosensitive leukaemic T cells and certain solid tumors. cytotoxic drugs mediate the induction of apoptosis by activation of the CD95/APO‐1/Fas system. Triggering of the corresponding signaling pathway may involve CD95‐receptor/ligand interaction, activation of caspases, or alterations in mitochondrial function. The purpose of our study was to determine if similar mechanisms are involved in the chemosensitivity of osteosarcomas. We found that cytotoxic drugs induce characteristic biochemical and morphological alterations related to apoptosis in osteosarcoma cell lines, including activation of caspases and disturbance of mitochondrial function. However, drug treatment did not result in activation of CD95‐receptor or CD95‐ligand mRNA. In addition, drug‐induced apoptosis was blocked by caspase inhibitors but not by inhibition of CD95‐ligand action, indicating a CD95‐receptor/ligand‐independent mechanism in osteosarcoma cell lines.