Laboratory of Computational Cell Biology, Department of Bio and Brain Engineering, KAIST, Daejeon, Korea.
Cancer Res Treat. 2009 Mar;41(1):36-44. doi: 10.4143/crt.2009.41.1.36. Epub 2009 Mar 31.
Malignant astrocytomas are among the commonest primary brain tumors and they have a grave prognosis, and so there is an urgent need to develop effective treatment. In this study, we investigated the molecular mechanisms that are responsible for the anti-tumor effect of ginsenosides on human astrocytoma cells.
We tested 13 different ginsenosides for their anti-tumor effect on human malignant astrocytoma cells in conjunction with Fas stimulation. In addition, the cell signaling pathways were explored by using pharmacological inhibitors and performing immunoblot analysis. DCF-DA staining and antioxidant experiments were performed to investigate the role of reactive oxygen species as one of the apoptosis-inducing mechanisms.
Among the 13 different ginsenoside metabolites, compound K and Rh(2) induced apoptotic cell death of the astrocytoma cells in a caspase- and p38 MAPK-dependent manner, yet the same treatment had no cytotoxic effect on the primary cultured human astrocytes. Combined treatment with ginsenosides and Fas ligand showed a synergistic cytotoxic effect, which was mediated by the reduction of intracellular reactive oxygen species.
These results suggest that ginsenoside metabolites in combination with Fas ligand may provide a new strategy to treat malignant astrocytomas, which are tumors that are quite resistant to conventional anti-cancer treatment.
恶性星形细胞瘤是最常见的原发性脑肿瘤之一，预后极差，因此迫切需要开发有效的治疗方法。本研究旨在探讨人参皂苷对人星形细胞瘤细胞的抗肿瘤作用的分子机制。
我们结合 Fas 刺激，测试了 13 种不同的人参皂苷对人恶性星形细胞瘤细胞的抗肿瘤作用。此外，还通过使用药理抑制剂和进行免疫印迹分析来探索细胞信号通路。通过 DCF-DA 染色和抗氧化实验，研究活性氧作为诱导细胞凋亡的机制之一的作用。
在 13 种不同的人参皂苷代谢物中，化合物 K 和 Rh2 以 caspase 和 p38 MAPK 依赖性方式诱导星形细胞瘤细胞的凋亡性细胞死亡，但相同的处理对原代培养的人星形胶质细胞没有细胞毒性作用。人参皂苷与 Fas 配体联合治疗显示出协同的细胞毒性作用，这是通过降低细胞内活性氧来介导的。
这些结果表明，人参皂苷代谢物与 Fas 配体联合使用可能为治疗对传统抗癌治疗相当耐药的恶性星形细胞瘤提供一种新策略。
