Changlong Li, Hezhen Wu, Yongping Huang, Yanfang Yang, Yanwen Liu, Jianwen Liu
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, PR China.
Biomed Pharmacother. 2008 Jul-Aug;62(6):401-9. doi: 10.1016/j.biopha.2007.10.010. Epub 2007 Nov 20.
6-O-Angeloylenolin, a sesquiterpene lactone from Centipeda minima, has been known to have anti-tumor activity against human colorectum, liver, stomach, lung, and skin tumor cells. However, its molecular mechanism is still obscure and insufficient in in vivo tests. In this study, we demonstrated that 6-O-angeloylenolin could induce apoptosis in human leukemia HL60 cells through stimulating the generation of reactive oxygen species, decreasing mitochondrial trans-membrane potential (DeltaPsim) and activating caspase-3/7. We also found that 6-O-angeloylenolin could inhibit nuclear translocation of NF-kappaB and modulate the expression of Bcl-2 gene family. These results indicated that 6-O-angeloylenolin induces apoptosis by inhibition of NF-kappaB activation, modulation of Bcl-2 gene family expression and destruction of mitochondrial function. Furthermore, we confirmed that 6-O-angeloylenolin could obviously inhibit the solid cancer growth in Lewis lung cancer xenograft models.
6-O-当归酰去甲蟛蜞菊内酯是一种来自最小鹅不食草的倍半萜内酯，已知对人结肠、肝脏、胃、肺和皮肤肿瘤细胞具有抗肿瘤活性。然而，其分子机制在体内试验中仍不清楚且不充分。在本研究中，我们证明6-O-当归酰去甲蟛蜞菊内酯可通过刺激活性氧的产生、降低线粒体跨膜电位（ΔΨm）和激活caspase-3/7来诱导人白血病HL60细胞凋亡。我们还发现6-O-当归酰去甲蟛蜞菊内酯可抑制NF-κB的核转位并调节Bcl-2基因家族的表达。这些结果表明，6-O-当归酰去甲蟛蜞菊内酯通过抑制NF-κB激活、调节Bcl-2基因家族表达和破坏线粒体功能来诱导细胞凋亡。此外，我们证实6-O-当归酰去甲蟛蜞菊内酯可明显抑制Lewis肺癌异种移植模型中的实体癌生长。
