齐墩果酸和熊果酸诱导四种人肝癌细胞系凋亡。

Oleanolic acid and ursolic acid induce apoptosis in four human liver cancer cell lines.

机构信息

Department and Graduate Program of BioIndustry Technology, Dayeh University, Changhua County, Taiwan, ROC.

出版信息

Toxicol In Vitro. 2010 Apr;24(3):842-8. doi: 10.1016/j.tiv.2009.12.008. Epub 2009 Dec 22.

DOI:10.1016/j.tiv.2009.12.008

PMID:20005942

Abstract

Apoptotic effects of oleanolic acid (OA) and ursolic acid (UA) on human liver cancer HepG2, Hep3B, Huh7 and HA22T cell lines were examined. OA or UA at 2, 4, 8 micromol/L were used and their effects on cell viability, DNA fragmentation, mitochondrial membrane potential (MMP), activity of Na(+)-K(+)-ATPase, caspase-3 and caspase-8, cell adhesion, level of intercellular adhesion molecule (ICAM)-1 and vascular endothelial growth factor (VEGF) in these cell lines were determined. OA or UA treatments concentration-dependently decreased cell viability and increased DNA fragmentation in HepG2 and Hep3B cell lines (P<0.05). However, these two compounds reduced viability and increased DNA fragmentation in Huh7 cell only at 4 and 8 micromol/L (P<0.05). OA or UA treatments concentration-dependently lowered MMP in HepG2, Hep3B and HA22T cell lines (P<0.05). These two compounds also concentration-dependently diminished Na(+)-K(+)-ATPase activity and VEGF level in four test cell lines (P<0.05). Besides Huh7 cell, OA or UA treatments concentration-dependently elevated caspase-3 and caspase-8 activities in other three cell lines (P<0.05). Besides HA22T cell, these two compounds concentration-dependently inhibited cell adhesion and decreased ICAM-1 level in other three cell lines (P<0.05). These findings support that OA and UA are potent anti-cancer agents to cause apoptosis in these liver cancer cell lines.

摘要

齐墩果酸（OA）和熊果酸（UA）对人肝癌 HepG2、Hep3B、Huh7 和 HA22T 细胞系的凋亡作用进行了研究。使用 2、4、8 μmol/L 的 OA 或 UA，测定其对细胞活力、DNA 片段化、线粒体膜电位（MMP）、Na(+)-K(+)-ATP 酶活性、caspase-3 和 caspase-8、细胞黏附、细胞间黏附分子（ICAM）-1 和血管内皮生长因子（VEGF）水平的影响。OA 或 UA 处理浓度依赖性地降低 HepG2 和 Hep3B 细胞系的细胞活力并增加 DNA 片段化（P<0.05）。然而，这两种化合物仅在 4 和 8 μmol/L 时降低 Huh7 细胞的活力并增加 DNA 片段化（P<0.05）。OA 或 UA 处理浓度依赖性地降低 HepG2、Hep3B 和 HA22T 细胞系的 MMP（P<0.05）。这两种化合物还浓度依赖性地降低了四个测试细胞系中的 Na(+)-K(+)-ATP 酶活性和 VEGF 水平（P<0.05）。除 Huh7 细胞外，OA 或 UA 处理浓度依赖性地增加了其他三种细胞系中的 caspase-3 和 caspase-8 活性（P<0.05）。除 HA22T 细胞外，这两种化合物浓度依赖性地抑制了其他三种细胞系的细胞黏附并降低了 ICAM-1 水平（P<0.05）。这些发现支持 OA 和 UA 是有效的抗癌剂，可引起这些肝癌细胞系发生凋亡。