Department of Pharmacy, Fujian University of Traditional Chinese Medicine, No. 1 Huatuo Road, Minhou Shangjie, Fuzhou, China.
Am J Chin Med. 2012;40(1):177-85. doi: 10.1142/S0192415X12500140.
Dehydrocorydaline is an alkaloid isolated from traditional Chinese herb Corydalis yanhusuo W.T. Wang. We discovered that it possessed anti-tumor potential during screening of anti-tumor natural products from Chinese medicine. In this study, its anti-tumor potential was investigated with breast cancer line cells MCF-7 in vitro. The anti-proliferative effect of dehydrocorydaline was determined by MTT assay and the mitochondrial membrane potential (Δ Ψ m) was monitored by JC-1 staining. DNA fragments were visualized by Hoechst 33342 staining and DNA ladder assay. Apoptotic related protein expressions were measured by Western blotting. Dehydrocorydaline significantly inhibited MCF-7 cell proliferation in a dose- dependent manner, which could be reversed by a caspase-8 inhibitor, Z-IETD-FMK. Dehydrocorydaline increased DNA fragments without affecting ΔΨm. Western blotting assay showed that dehydrocorydaline dose-dependently increased Bax protein expression and decreased Bcl-2 protein expression. Furthermore, dehydrocorydaline induced activation of caspase-7,-8 and the cleavage of PARP without affecting caspase-9. These results showed that dehydrocorydaline inhibits MCF-7 cell proliferation by inducing apoptosis mediated by regulating Bax/Bcl-2, activating caspases as well as cleaving PARP.
脱氢紫堇碱是一种从传统中药延胡索中分离得到的生物碱。我们在筛选中药抗肿瘤天然产物时发现其具有抗肿瘤活性。本研究采用体外 MCF-7 乳腺癌细胞系考察了脱氢紫堇碱的抗肿瘤活性。MTT 法测定脱氢紫堇碱的抗增殖作用,JC-1 染色监测线粒体膜电位(ΔΨm)。Hoechst 33342 染色和 DNA 梯带实验观察 DNA 片段化。Western blot 检测凋亡相关蛋白表达。结果表明,脱氢紫堇碱呈剂量依赖性抑制 MCF-7 细胞增殖,该作用可被 caspase-8 抑制剂 Z-IETD-FMK 逆转。脱氢紫堇碱增加 DNA 片段化,不影响 ΔΨm。Western blot 结果显示,脱氢紫堇碱呈剂量依赖性增加 Bax 蛋白表达,降低 Bcl-2 蛋白表达。此外,脱氢紫堇碱诱导 caspase-7、-8 活化和 PARP 切割,而不影响 caspase-9。这些结果表明,脱氢紫堇碱通过调节 Bax/Bcl-2 诱导细胞凋亡,激活 caspase 以及切割 PARP 抑制 MCF-7 细胞增殖。