Derivate isocorydine inhibits cell proliferation in hepatocellular carcinoma cell lines by inducing G2/M cell cycle arrest and apoptosis | |
Department | 中科院西北特色植物资源化学重点实验室/甘肃省天然药物重点实验室 |
Chen, Lijuan1,2; Tian, Hua2; Li, Meng1,2; Ge, Chao2; Zhao, Fangyu2; Zhang, Lixing2; Li, Hong2; Liu JX(柳军玺)3; Wang, Tingpu4; Yao, Ming2; Li, Jinjun2 | |
2016 | |
Source Publication | Tumor Biology |
ISSN | 1010-4283 |
Volume | 37Issue:5Pages:5951-5961 |
Abstract | We have previously demonstrated that isocorydine (ICD) can be served as a potential antitumor agent in hepatocellular carcinoma (HCC). A novel derivate of isocorydine (d-ICD) could significantly improve its anticancer activity in tumors. However, the molecular mechanisms of d-ICD on HCC cells remain to be unclear. In this study, we observed that d-ICD inhibited cell proliferation and induced apoptosis of HCC cells in a concentration-dependent manner. We found d-ICD induced G2/M cycle arrest of HCC cells via DNA damage 45 alpha (GADD45A) and p21 pathway in vitro and in vivo. In d-ICD-treated cells, cell cycle-related proteins cyclin B1 and p-CDC2 were upregulated and p-cyclin B1, CDC2, and E2F1 were inhibited. p21 expression can be reversed by knockdown of GADD45A in d-ICD-treated HCC cells. Enforced expression of CCAAT/enhancer-binding protein β (C/EBPβ) in combination with d-ICD enhanced the p21 expression in HCC cells. Furthermore, the luciferase reporter assay showed that upregulation of GADD45A by C/EBPβ was achieved through the increase of GADD45A promoter activity. These findings indicate that d-ICD inhibits cell proliferation and induces cell cycle arrest through activation of C/EBPβ-GADD45A-p21 pathway in HCC cells. d-ICD might be a promising chemotherapeutic agent for the treatment of HCC. |
Keyword | D-icd Cell Cycle Gadd45a Hepatocellular Carcinoma |
Subject Area | 分析化学与药物化学 |
DOI | 10.1007/s13277-015-4362-6 |
Funding Organization | the National Key Program for Basic Research of China (973) (2015CB553905);National Natural Science Foundation of China (81272438;81472726;81472570;81372192;31360603);Key Discipline and Specialty Foundation of Shanghai Municipal Commission of Health and Family Planning, the National Key Sci-Tech Special Project of China (2013ZX10002-011);Innovation Program of Shanghai Municipal Education Commission (13ZZ082);the SKLORG Research foundation (91-13-02;91-14-09) |
Indexed By | SCI |
If | 2.926 |
Language | 英语 |
Funding Project | 药物工艺标准研究组 |
compositor | 第三作者单位 |
Citation statistics | |
Document Type | 期刊论文 |
Identifier | http://ir.licp.cn/handle/362003/20111 |
Collection | 中科院西北特色植物资源化学重点实验室/甘肃省天然药物重点实验室 |
Corresponding Author | Li, Jinjun |
Affiliation | 1.Shanghai Med Coll, ShaFudan Univ, Shanghai, China 2.State Key Lab Oncogenes & Related Genes, Shanghai Canc Inst., Renji Hosp, Jiaotong Univ, Sch Med, Shanghai, China 3.Key Lab Chem Northwestern Plant Resources and Key Lab Fornatural Med Gansu Prov,Lanzhou Inst Chem Phys, Chinese Acad Sci, Lanzhou Inst Chem Phys, Lanzhou China 4.Coll Life Sci & Chem, Tianshui Normal Univ, Tianshui, China |
Recommended Citation GB/T 7714 | Chen, Lijuan,Tian, Hua,Li, Meng,et al. Derivate isocorydine inhibits cell proliferation in hepatocellular carcinoma cell lines by inducing G2/M cell cycle arrest and apoptosis[J]. Tumor Biology,2016,37(5):5951-5961. |
APA | Chen, Lijuan.,Tian, Hua.,Li, Meng.,Ge, Chao.,Zhao, Fangyu.,...&Li, Jinjun.(2016).Derivate isocorydine inhibits cell proliferation in hepatocellular carcinoma cell lines by inducing G2/M cell cycle arrest and apoptosis.Tumor Biology,37(5),5951-5961. |
MLA | Chen, Lijuan,et al."Derivate isocorydine inhibits cell proliferation in hepatocellular carcinoma cell lines by inducing G2/M cell cycle arrest and apoptosis".Tumor Biology 37.5(2016):5951-5961. |
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