著者

山崎 正利 池並 通裕 来生 淳 油井 聡 安部 茂 水野 伝一

出版者

公益社団法人日本薬学会

雑誌

薬学雑誌 (ISSN:00316903)

巻号頁・発行日

vol.104, no.7, pp.p769-774, 1984-07

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The present study shows that some selected anti-cancer drugs induce tumor lysis in vitro in cooperation with phagocytic cells (drug-dependent cellular cytotoxicity ; DDCC) and that chemotherapeutic drugs augment the mediator-dependent killing activity of macrophages. Tumor cells pretreated with the drugs were susceptible to phagocytemediated killing. Tumor necrosis serum can also cooperate with some drugs in killing tumor cells. Moreover, some selected drugs can induce cytotoxic macrophages and the quantitative changes of phagocytes such as polymorphonuclear leukocytes. These results suggest that some anti-cancer drugs have the activities of inactivation of tumor cells and/or activation of host cells. Thus, tumor cells may be killed effectively in vivo by anti-cancer drugs through these mechanisms.

著者

油井 聡 三上 正彰 三巻 祥浩 指田 豊 山崎 正利

出版者

公益社団法人日本薬学会

雑誌

藥學雜誌 (ISSN:00316903)

巻号頁・発行日

vol.121, no.2, pp.167-171, 2001-02-01

被引用文献数

22

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We previously demonstrated that Amaryllidaceae alkaloids, lycorine and lycoricidinol, inhibit induction of apoptosis by calprotectin derived from neutrophils, and that the latter alkaloid showed suppression in rat adjuvant-induced arthritis model. These findings suggest that the alkaloids have a modulating activity against inflammatory reaction. To explore further the mechanism of the suppression for inflammation, we studied the effect of the alkaloids on macrophage tumor necrosis factor(TNF-α) production in vitro, since TNF-α is recognized as a pivotal cytokine to regulate inflammation. As a result of this study, lycorine and lycoricidinol inhibited TNF-α production of murine macrophages stimulated with lipopolysaccharide(ID_<50> were 0.2μg/ml and 0.002μg/ml, respectively). The inhibition was also observed in macrophages treated by Gram-positive bacteria, Enterococcus faecalis. Both lycorine and lycoricidinol reportedly have inhibitory activity for protein biosynthesis. Although the inhibition of TNF-α production by lycoricidinol was mainly due to the inhibition of protein biosynthesis, lycorine showed inhibition against TNF-α prodictuon at lower concentrations than the case that they inhibited ^<35>S-Cysteine/^<35>S-Methionine incorporation into macrophages. These facts sugges that the inhibition of TNF-α production is not due to the inhibitory activity against protein translation at least at lower concentrations. From these results, it was concluded that these alkaloids exert inhibitory effects not only on neutrophil apoptosis-inducing protein, calprotectin, but also on macrophage TNF-α production.