Phenylethanoid glycosides as a new macrophage-activating factor

Acteoside是一种苯丙素类糖苷，可诱导巨噬细胞或SV4O转化内皮细胞(Gen-T)产生细胞因子和表达黏附分子。另一方面，Acteoside对多种肿瘤细胞具有明显的细胞毒作用。在本研究中，我们研究了细胞激活和细胞死亡的信号转导途径是否不同。Acteoside在加入培养基后1min即可产生过氧化氢，用夹带法检测到过氧化氢的产生。过氧化氢的产生依赖于Acteoside的量，并被过氧化氢酶预处理所消除。当检测过氧化氢的产生量与对肿瘤细胞的杀伤强度之间的关系时，以产生的过氧化氢的量来诱导细胞死亡。此外，过氧化氢酶可完全抑制Acteoside诱导的细胞死亡。而Acteoside对Gen-T细胞黏附分子的表达无明显影响，提示过氧化氢不参与Acteoside激活Gen-T细胞的信号转导。到目前为止，我们认为活性氧物种、细胞内钙和蛋白质磷酸化是烟碱苷诱导的信号转导的第二信使，而烟碱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否定。其确切的信号转导机制还有待于进一步阐明。

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.