College of Life Sciences, Southwest Forestry University, Kunming, Yunnan 650224, P.R. China.
Basic Medical College, Yunnan University of Traditional Chinese Medicine, Kunming, Yunnan 650500, P.R. China.
Mol Med Rep. 2018 Mar;17(3):3527-3536. doi: 10.3892/mmr.2017.8328. Epub 2017 Dec 20.
The roots of Codonopsis cordifolioidea (classified as campanulaceae cordifolioidea), locally known as Tsoong, have been used as a tonic food. The major components isolated from Tsoong have been demonstrated to present anti‑human immunodeficiency virus‑1 activities and cytotoxicity against various tumor cell lines. However, the possible effects of the novel compound isolated from Tsoong, cordifoliketones A, on pancreatic ductal adenocarcinoma (PDAC) cells, are still unknown. In the present study, cordifoliketones A extractions were prepared from Tsoong, and the possible effects on PDAC cell growth, apoptosis, migration and invasion in vitro and in vivo were exlored. The cytotoxicity assay, apoptosis assay, western blotting, migration and invasion assay, and a PDAC cell (AsPC‑1, BxPC‑3 and PANC‑1) xenograft mice model were employed. The results demonstrated that treatment with cordifoliketones A: i) inhibited proliferation and promoted apoptosis of PDAC cells; ii) significantly induced apoptosis and altered expression of apoptosis‑associated proteins in a dose‑dependent manner; iii) suppressed migration and invasion of PDAC cells in a dose‑dependent manner; and iv) restrained the growth of PDAC neoplasm in nude mice. Furthermore, cordifoliketones A demonstrated non‑cytotoxic activity in a panel of normal human cells, including hTERT‑HPNE, 293, hepatocyte HL‑7702 and HL‑1 cells. Therefore, these data indicated that cordifoliketones A may be a potential candidate compound for the prevention of PDAC cell proliferation and metastasis, presumably by induction apoptosis and inhibiting viability, invasion and migration of PDAC cells.
紫菀(归类为桔梗科紫菀属)的根,俗称紫菀,被用作滋补食品。从紫菀中分离得到的主要成分已被证明具有抗人类免疫缺陷病毒-1 活性和对多种肿瘤细胞系的细胞毒性。然而,紫菀中分离得到的新型化合物——紫菀酮 A 对胰腺导管腺癌(PDAC)细胞的可能影响尚不清楚。在本研究中,从紫菀中提取紫菀酮 A,并探讨其对 PDAC 细胞体外和体内生长、凋亡、迁移和侵袭的可能影响。采用细胞毒性测定、凋亡测定、Western blot 分析、迁移和侵袭测定以及 PDAC 细胞(AsPC-1、BxPC-3 和 PANC-1)异种移植小鼠模型进行研究。结果表明,紫菀酮 A 处理:i)抑制 PDAC 细胞增殖并促进其凋亡;ii)以剂量依赖性方式显著诱导凋亡并改变凋亡相关蛋白的表达;iii)以剂量依赖性方式抑制 PDAC 细胞的迁移和侵袭;iv)抑制裸鼠 PDAC 肿瘤的生长。此外,紫菀酮 A 在一组正常人类细胞(包括 hTERT-HPNE、293、肝细胞 HL-7702 和 HL-1 细胞)中表现出非细胞毒性活性。因此,这些数据表明,紫菀酮 A 可能是预防 PDAC 细胞增殖和转移的潜在候选化合物,可能通过诱导凋亡和抑制 PDAC 细胞的活力、侵袭和迁移来实现。