Induction of cell cycle arrest and apoptosis by tomentosin in hepatocellular carcinoma HepG2 and Huh7 cells

被引：19
作者：
Yu, S. H. [1 ]
Lee, C. M. [1 ]
Ha, S. H. [2 ]
Lee, J. [3 ]
Jang, K. Y. [4 ,5 ,6 ]
Park, S. H. [1 ]
机构：
[1] Hongik Univ, Dept Bio & Chem Engn, Sejong 30016, South Korea
[2] Jeonbuk Natl Univ, Div Biotechnol, Iksan, South Korea
[3] Sungkyunkwan Univ, Dept Integrat Biotechnol, Suwon 16419, South Korea
[4] Jeonbuk Natl Univ, Med Sch, Dept Pathol, Jeonju 54896, South Korea
[5] Jeonbuk Natl Univ, Res Inst Clin Med, Jeonju 54896, South Korea
[6] Jeonbuk Natl Univ Hosp, Biomed Res Inst, Jeonju 54896, South Korea
来源：
HUMAN & EXPERIMENTAL TOXICOLOGY | 2021年 / 40卷 / 02期
基金：
新加坡国家研究基金会;
关键词：
Tomentosin; hepatocellular carcinoma; FOXO3; p53; cell cycle arrest; apoptosis; PLANT-EXTRACTS; INULA-VISCOSA; HEART-DISEASE; CANCER; P53; PATHWAYS; JNK; MECHANISMS; RESISTANCE; MORTALITY;
D O I：
10.1177/0960327120943935
中图分类号：
R99 [毒物学（毒理学）];
学科分类号：
100405 ;
摘要：
Tomentosin, a sesquiterpene lactone, is known to possess various biological activities. However, its anticarcinogenic activity against human hepatocellular carcinoma (HCC) cells has not been investigated in detail. Thus, this study aimed to elucidate the cytotoxic mechanism of tomentosin in human HCC cell lines HepG2 and Huh7. WST-1, cell counting, and colony formation assay results showed that treatment with tomentosin decreased the viability and suppressed the proliferation rate of HepG2 and Huh7 cells in a dose- and time-dependent manner. Cell cycle analysis revealed increased population of cells at the SubG1 and G2/M stage, and decreased population of cells at the G0/1 stage in HepG2 and Huh7 cells treated with tomentosin. Annexin V/propidium iodide double staining and TUNEL assay results showed increased apoptotic cell population and DNA fragmentation in HepG2 and Huh7 cells treated with tomentosin. Western blotting analysis results showed that tomentosin treatment significantly increased the expression level of Bax, Bim (short form), cleaved PARP1, FOXO3, p53, pSer15p53, pSer20p53, pSer46p53, p21, and p27, but decreased the expression of Bcl2, caspase3, caspase7, caspase9, cyclin-dependent kinase 2 (CDK2), CDK4, CDK6, cyclinB1, cyclinD1, cyclinD2, cyclinD3, and cyclinE in a dose-dependent manner. Taken together, this study revealed that tomentosin, which acted through cell cycle arrest and apoptosis, may be a useful therapeutic option against HCC.
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收藏
页码：231 / 244
页数：14
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