Anti-tumor Activity of Daphne mucronata Extract and its Effects on TNF-alpha Receptors and TNF-alpha Release in Cultured Human Monocytes

摘要

Oral administration of an alcohol extract (EtOH: H_2O 1:1 v/v) of Daphne mucronata (Thymelaeaceae) to a group of breast tumor bearing rats, for more than 20 consecutive days, reduced significantly the diameter of tum'or or eliminated them totally if the treatment continued for a longer time. The breast tumors were induced in rats by DMBA administration (5mg per dose) twice a week and for 4 consecutive weeks. To gain insight into the mode of action of this anti-neoplastic plant, the effects of the plant extract were evaluated on the human tumor necrosis factor alpha (hTNF-a) release and TNF-a receptor regulation in the cultured human monocytes in the presence or absence of bacterial lipo-polysaccharide (LPS). The data indicated that the plant extract at various doses, like Taxol, did slightly increase TNF-a secretion by the cultured monocytes. In addition, both Taxol and the plant extract down-regulated the TNF-a receptors in a time dependent manner. In less than 2 h, under the influence of stimuli (Daphne mucronata extract or Taxol), the number of TNF-a receptors reduced to a non-detectable level using ~(125)I-TNF-a binding assay. These data probably support the down-regulation of TNF-a receptors by the Daphne mucronata extract by a mechanism similar to Taxol.