Receptor activator of nuclear factor kappaB ligand plays a nonredundant role in doxorubicin-induced apoptosis
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Receptor activator of nuclear factor kappaB ligand plays a nonredundant role in doxorubicin-induced apoptosis. / Müller, Ingo; Pfister, Stefan M; Grohs, Ulrike; Zweigner, Janine; Handgretinger, Rupert; Niethammer, Dietrich; Bruchelt, Gernot.
In: CANCER RES, Vol. 63, No. 8, 15.04.2003, p. 1772-5.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Receptor activator of nuclear factor kappaB ligand plays a nonredundant role in doxorubicin-induced apoptosis
AU - Müller, Ingo
AU - Pfister, Stefan M
AU - Grohs, Ulrike
AU - Zweigner, Janine
AU - Handgretinger, Rupert
AU - Niethammer, Dietrich
AU - Bruchelt, Gernot
PY - 2003/4/15
Y1 - 2003/4/15
N2 - Doxorubicin induces apoptosis in a variety of cells. We investigated the expression and function of various tumor necrosis factor (TNF)alpha-homologues and their receptors. CEM cells did not differentially express any one of the TNFalpha-homologous receptors investigated nor TNF-related apoptosis-inducing ligand or TNF-related weakly apoptosis-inducing ligand (TWEAK) in the presence of doxorubicin. In addition to CD95 ligand, however, receptor activator of nuclear factor kappaB ligand (RANKL) was strongly up-regulated. Doxorubicin-induced apoptosis was greatly suppressed in the presence of either neutralizing antibody or RANK-Fc fusion protein. Moreover, neutralizing RANKL also prevented cytochrome c release from mitochondria. RANKL alone was unable to induce significant levels of apoptosis in CEM cells. However, doxorubicin-induced apoptosis was increased >2-fold when exogenous RANKL was added. Therefore, RANKL is necessary but not sufficient to account for early doxorubicin-induced apoptosis in CEM cells. This finding suggests improved chemotherapeutic efficiency of the anthracyclin against susceptible malignant cells in the presence with RANKL.
AB - Doxorubicin induces apoptosis in a variety of cells. We investigated the expression and function of various tumor necrosis factor (TNF)alpha-homologues and their receptors. CEM cells did not differentially express any one of the TNFalpha-homologous receptors investigated nor TNF-related apoptosis-inducing ligand or TNF-related weakly apoptosis-inducing ligand (TWEAK) in the presence of doxorubicin. In addition to CD95 ligand, however, receptor activator of nuclear factor kappaB ligand (RANKL) was strongly up-regulated. Doxorubicin-induced apoptosis was greatly suppressed in the presence of either neutralizing antibody or RANK-Fc fusion protein. Moreover, neutralizing RANKL also prevented cytochrome c release from mitochondria. RANKL alone was unable to induce significant levels of apoptosis in CEM cells. However, doxorubicin-induced apoptosis was increased >2-fold when exogenous RANKL was added. Therefore, RANKL is necessary but not sufficient to account for early doxorubicin-induced apoptosis in CEM cells. This finding suggests improved chemotherapeutic efficiency of the anthracyclin against susceptible malignant cells in the presence with RANKL.
KW - Antibiotics, Antineoplastic
KW - Apoptosis
KW - Carrier Proteins
KW - Cell Line
KW - Cytochrome c Group
KW - Doxorubicin
KW - Drug Synergism
KW - Humans
KW - Membrane Glycoproteins
KW - Mitochondria
KW - NF-kappa B
KW - RANK Ligand
KW - Receptor Activator of Nuclear Factor-kappa B
KW - Staurosporine
KW - T-Lymphocytes
KW - Tumor Necrosis Factor-alpha
M3 - SCORING: Journal article
C2 - 12702561
VL - 63
SP - 1772
EP - 1775
JO - CANCER RES
JF - CANCER RES
SN - 0008-5472
IS - 8
ER -