Zhang Shou-De, Shan Lei, Li Wei, Li Hong-Lin, Zhang Wei-Dong
Shanghai Key Laboratory of New Drug Design, State Key Laboratory of Bioreactor Engineering, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
Chin J Nat Med. 2015 Sep;13(9):660-6. doi: 10.1016/S1875-5364(15)30063-7.
The biflavonoid isochamaejasmin is mainly distributed in the root of Stellera chamaejasme L. (Thymelaeaceae) that is used in traditional Chinese medicine (TCM) to treat tumors, tuberculosis, and psoriasis. Herein, isochamaejasmin was found to show similar bioactivity against Bcl-2 family proteins to the reference Bcl-2 ligand (-)-gossypol through 3D similarity search. It selectively bound to Bcl-xl and Mcl-1 with Ki values being 1.93 ± 0.13 μmol·L(-1) and 9.98 ± 0.21 μmol·L(-1), respectively. In addition, isochamaejasmin showed slight growth inhibitory activity against HL-60 with IC50 value being 50.40 ± 1.21 μmol·L(-1) and moderate growth inhibitory activity against K562 cells with IC50 value being 24.51 ± 1.62 μmol·L(-1). Furthermore, isochamaejasmin induced apoptosis of K562 cells by increasing the intracellular expression levels of proteins of the cleavage of caspase-9, caspase-3, and PARP which involved in the Bcl-2-induced apoptosis pathway. These results indicated that isochamaejasmin induces apoptosis in leukemia cells by inhibiting the activity of Bcl-2 family proteins, providing evidence for further studying the underlying anti-cancer mechanism of S. chamaejasme L.
双黄酮异狼毒素主要分布于瑞香科植物狼毒（Stellera chamaejasme L.）的根部，该植物在传统中药中用于治疗肿瘤、结核病和牛皮癣。在此，通过三维相似性搜索发现异狼毒素对Bcl-2家族蛋白显示出与参考Bcl-2配体（-）-棉酚相似的生物活性。它选择性地与Bcl-xl和Mcl-1结合，Ki值分别为1.93±0.13μmol·L（-1）和9.98±0.21μmol·L（-1）。此外，异狼毒素对HL-60细胞显示出轻微的生长抑制活性，IC50值为50.40±1.21μmol·L（-1），对K562细胞显示出中等的生长抑制活性，IC50值为24.51±1.62μmol·L（-1）。此外，异狼毒素通过增加参与Bcl-2诱导的凋亡途径的caspase-9、caspase-3和PARP裂解蛋白的细胞内表达水平，诱导K562细胞凋亡。这些结果表明，异狼毒素通过抑制Bcl-2家族蛋白的活性诱导白血病细胞凋亡，为进一步研究狼毒潜在的抗癌机制提供了证据。
