Yan Feng, Liu Yang, Wang Wenbo
Department of Bone Surgery, First Affiliated Hospital of Harbin Medical University, No. 23 Youzheng Street, Harbin, Heilongjiang Province, 150001, China.
Tumour Biol. 2013 Aug;34(4):2135-40. doi: 10.1007/s13277-013-0744-9. Epub 2013 Apr 16.
Matrine, one of the main active components of the extracts from the dry roots of Sophora flavescens, has a potent antitumor activity in vitro and in vivo. However, the molecular mechanism of cell apoptosis induced by matrine remains elusive. Here, we investigated the apoptosis in matrine-treated rat osteosarcoma UMR-108 cells. The results showed that matrine could inhibit cell proliferation and induce apoptosis in a dose- and time-dependent manner. Further investigation revealed a disruption of mitochondrial transmembrane potential and an upregulation of reactive oxygen species in matrine-treated cells. By western blot analysis, we found the upregulation of cleaved poly(ADP-ribose) polymerase, cleaved caspase-3, and cleaved caspase-9 and the downregulation of Bax/Bcl-2 with different concentrations of matrine. These protein interactions may play a pivotal role in the regulation of apoptosis. Taken together, these results overall indicate that matrine could be used as an effective antitumor agent in therapy of osteosarcoma targets the caspase-dependent signaling pathway.
苦参碱是苦参干燥根提取物的主要活性成分之一，在体外和体内均具有强大的抗肿瘤活性。然而，苦参碱诱导细胞凋亡的分子机制仍不清楚。在此，我们研究了苦参碱处理的大鼠骨肉瘤UMR - 108细胞中的细胞凋亡情况。结果表明，苦参碱能够以剂量和时间依赖性方式抑制细胞增殖并诱导凋亡。进一步研究发现，苦参碱处理的细胞中线粒体跨膜电位破坏，活性氧上调。通过蛋白质印迹分析，我们发现不同浓度的苦参碱可使裂解的聚（ADP - 核糖）聚合酶、裂解的半胱天冬酶 - 3和裂解的半胱天冬酶 - 9上调，以及Bax/Bcl - 2下调。这些蛋白质相互作用可能在细胞凋亡调控中起关键作用。综上所述，这些结果总体表明苦参碱可作为一种有效的抗肿瘤药物用于骨肉瘤治疗，其靶向半胱天冬酶依赖性信号通路。
