Phenylethanoid glycosides as a new macrophage-activating factor

牛皮苷是一种苯丙苷，可诱导巨噬细胞或sv40转化内皮细胞（GEN-T）的细胞因子产生和粘附分子表达。另一方面，毛蕊花苷对多种肿瘤细胞均表现出细胞毒性。在本研究中，我们研究了信号转导在细胞活化和细胞死亡中的途径是否不同。牛蒡子苷在加入培养基1 min后产生过氧化氢，用scoppletin法检测。过氧化氢的生成依赖于乙酰糖苷的量，过氧化氢酶预处理使过氧化氢消失。研究过氧化氢的产生量与肿瘤细胞毒性强度的关系，发现过氧化氢的产生量可以诱导肿瘤细胞死亡。此外，过氧化氢酶完全抑制毛蕊糖苷诱导的细胞死亡。相比之下，过氧化氢酶预处理不影响毛蕊糖苷在GEN-T细胞上的细胞粘附分子表达，这表明过氧化氢不参与毛蕊糖苷活化GEN-T细胞的信号转导。到目前为止，我们认为活性氧、细胞内钙和蛋白质磷酸化是由毛蕊花苷引发的信号转导的第二信使，而毛蕊花苷衍生的过氧化氢和过氧化氢介导的磷酸化将被上述事实所否定。信号转导的确切机制有待进一步研究。

Acteoside, a phenylpropanoid glycoside, was found to induce cytokine production and adhesion molecule expression on macrophages or SV4O-transformed endothelial cells (GEN-T). On the other hand, acteoside showed cytotoxicity against various kinds of tumor cells. In this study we studied whether the pathway of signal transduction in cell activation and cell death was different or not. Acteoside produced hydrogen peroxide which was detected by scopletin method as early as 1 min after its addition into medium. Its hydrogen peroxide production was dependent on the amount of acteoside and was abolished by the pretreatment with catalase. When the relationship between the amount of produced hydrogen peroxide and the intensity of cytotoxicity against tumor cells was examined, cell death was induced with the amount of produced hydrogen peroxide. In addition catalase completely inhibited acteoside-induced cell death. In contrast, cell adhesion molecule expression on GEN-T cells by acteoside was not influenced by pretreatment with catalase, suggesting that hydrogen peroxide was not implicated in the signal transduction of GEN-T cell activation by acteoside. We so far considered reactive oxygen species, intracellular calcium and protein phosphorylation as second messenger of signal transduction elicited by acteoside, whereas acteoside-derived hydrogen peroxide, and phosphorylation mediated by hydrogen peroxide would be negated by the facts described above. The precise mechanism of signal transduction remains to be clarified in the future.