Synergistic effect of tumor necrosis factor-alpha and interferon-alpha on the induction of apoptosis detected by BM-1/JIMRO: a new marker of apoptosis.
The effects of the combination of natural human tumor necrosis factor-alpha (nHuTNF-alpha) and natural human interferon-alpha (nHuIFN-alpha) on the induction of apoptosis were investigated by immunohistochemical analysis with BM-1/JIMRO monoclonal antibody in RPMI 4788 tumor cells. Few tumor cells in the control culture could spontaneously undergo apoptosis. The number of positive cells increased at 2 and 4 h after treatment with nHuTNF-alpha (1 x 10(5) U/ml) and nHulFN-alpha (1 x 10(5) IU/ml). This effect was clearly maintained from 8 h up to 72 h of culture. The number of apoptotic cells also greatly increased with doses, suggesting that the apoptosis induced by nHuTNF-alpha and nHuIFN-alpha in combination was dose-dependent. nHuTNF-alpha or nHuIFN-alpha alone could induce apoptosis, but the induction increased significantly when the two cytokines were combined. These findings indicate that by combining nHuTNF-alpha and nHuIFN-alpha apoptosis can be synergistically induced in RPMI 4788 tumor cells, and may have specific therapeutic implications for clinical treatments using these two cytokines.
Zhang
W
W
First Department of Surgery, Okayama University Medical School, Japan.
Naomoto
Y
Y
Tanaka
N
N
Hizuta
A
A
Orita
K
K
D000911:Antibodies, Monoclonal; D017209:Apoptosis / Q000187:drug effects*; D015415:Biomarkers; D003110:Colonic Neoplasms / Q000473:pathology; D004357:Drug Synergism; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D015415:Biomarkers; D016898:Interferon-alpha; D014409:Tumor Necrosis Factor-alpha