Ko Seong-Gyu, Koh Seung-Hee, Jun Chan-Yong, Nam Chang-Gyu, Bae Hyun-Su, Shin Min-Kyu
Department of Tumor Biology, Cancer Research Institute, College of Medicine, Seoul National University, Yongon-dong, Chongno-gu, Korea.
Biol Pharm Bull. 2004 Oct;27(10):1604-10. doi: 10.1248/bpb.27.1604.
We performed this study to understand the molecular basis underlying the antitumor effects of Saussurea lappa, Pharbitis nil, Plantago asiatica and Taraxacum mongolicum, which have been used for herbal medicinal treatments against cancers in East Asia. We analyzed the effects of these medicinal herbs on proliferation and on expression of cell growth/apoptosis related molecules, with using an AGS gastric cancer cell line. The treatments of Saussurea lappa and Pharbitis nil dramatically reduced cell viabilities in a dose and time-dependent manner, but Plantago asiatica and Taraxacum mongolicum didn't. FACS analysis and Annexin V staining assay also showed that both Saussurea lappa and Pharbitis nil induce apoptotic cell death of AGS. Expression analyses via RT-PCR and Western blots revealed that Saussurea lappa, but not Pharbitis nil, increased expression of the p53 and its downstream effector p21Waf1, and that the both increased expression of apoptosis related Bax and cleavage of active caspase-3 protein. We also confirmed the translocation of Bax to mitochondria. Collectively, our data demonstrate that Saussurea lappa and Pharbitis nil induce growth inhibition and apoptosis of human gastric cancer cells, and these effects are correlated with down- and up-regulation of growth-regulating apoptotic and tumor suppressor genes, respectively.
我们开展这项研究，以了解木香、牵牛子、车前草和蒲公英的抗肿瘤作用的分子基础，这些植物在东亚一直被用作抗癌草药治疗。我们使用AGS胃癌细胞系，分析了这些草药对细胞增殖以及细胞生长/凋亡相关分子表达的影响。木香和牵牛子处理以剂量和时间依赖性方式显著降低细胞活力，但车前草和蒲公英则不然。流式细胞术分析和膜联蛋白V染色试验还表明，木香和牵牛子均诱导AGS细胞发生凋亡性细胞死亡。通过逆转录聚合酶链反应（RT-PCR）和蛋白质免疫印迹法进行的表达分析显示，木香而非牵牛子增加了p53及其下游效应分子p21Waf1的表达，且二者均增加了凋亡相关蛋白Bax的表达以及活性半胱天冬酶-3蛋白的裂解。我们还证实了Bax向线粒体的转位。总体而言，我们的数据表明，木香和牵牛子诱导人胃癌细胞生长抑制和凋亡，且这些效应分别与生长调节凋亡基因和肿瘤抑制基因的下调及上调相关。
