Xing Shao-Fang, Liu Lin-Hua, Zu Ma-Li, Lin Man, Zhai Xin-Fang, Piao Xiang-Lan
School of Pharmacy, Minzu University of China, Beijing, China.
Key Laboratory of Ethnomedicine (MINZU University of China), Ministry of Education, Beijing, China.
Planta Med. 2019 Mar;85(5):394-405. doi: 10.1055/a-0810-7738. Epub 2018 Dec 18.
Damulin B, a dammarane-type saponin from steamed , exhibits the strongest activity against human lung carcinoma A549 cells among the isolated active saponins. In this study, the structure-activity relationship of a series of saponin compounds was discussed. The inhibitory effect of damulin B on human lung cancer A549 and H1299 cells was investigated from apoptosis, cell cycle, and migration aspects. , human lung cancer cells were more susceptible to damulin B treatment than human normal fibroblasts. Damulin B exhibited a strong cytotoxic effect, as evidenced by the increase of apoptosis rate, reduction of mitochondrial membrane potential (MMP), generation of reactive oxygen species, and G0/G1 phase arrest. Furthermore, damulin B activated the following: both intrinsic and extrinsic apoptosis pathways along with early G1 phase arrest via the upregulation of the Bax, Bid, tBid, cleaved caspase-8, and p53 expression levels; downregulation of the procaspase-8/-9, CDK4, CDK6, and cyclin D1 expression levels; and more release of cytochrome c in the cytoplasm. In addition, antimigratory activities and suppressive effects on metastasis-related factors, such as MMP-2 and MMP-9, accompanied by the upregulation of IL-24 were revealed. Altogether, the results proved that damulin B could inhibit human lung cancer cells by inducing apoptosis, blocking the cell cycle at early G0/G1 phase and suppressing the migration. Hence, damulin B has potential therapeutic efficacy against lung cancer.
达木林B是一种从蒸制物中提取的达玛烷型皂苷，在分离得到的活性皂苷中，它对人肺癌A549细胞表现出最强的活性。在本研究中，探讨了一系列皂苷化合物的构效关系。从细胞凋亡、细胞周期和迁移等方面研究了达木林B对人肺癌A549和H1299细胞的抑制作用。结果表明，人肺癌细胞比人正常成纤维细胞对达木林B处理更敏感。达木林B表现出强烈的细胞毒性作用，表现为凋亡率增加、线粒体膜电位（MMP）降低、活性氧生成以及G0/G1期阻滞。此外，达木林B激活了以下过程：通过上调Bax、Bid、tBid、裂解的caspase-8和p53的表达水平，激活内源性和外源性凋亡途径以及早期G1期阻滞；下调procaspase-8/-9、CDK4、CDK6和细胞周期蛋白D1的表达水平；以及细胞质中细胞色素c的更多释放。此外，还发现了抗迁移活性以及对转移相关因子（如MMP-2和MMP-9）的抑制作用，并伴随着IL-24的上调。总之，结果证明达木林B可通过诱导凋亡、在早期G0/G1期阻断细胞周期和抑制迁移来抑制人肺癌细胞。因此，达木林B对肺癌具有潜在的治疗效果。
