Inhibitive effects of 15-deoxy-Δ12,14-prostaglandin J2 on hepatoma-cell proliferation through reactive oxygen species-mediated apoptosis

被引:8
作者
Chen, Kan [1 ]
Dai, Weiqi [1 ]
Wang, Fan [1 ]
Xia, Yujing [1 ]
Li, Jingjing [1 ]
Li, Sainan [1 ]
Liu, Tong [1 ]
Zhang, Rong [2 ]
Wang, Jianrong [2 ]
Lu, Wenxia [2 ]
Zhou, Yuqing [3 ]
Yin, Qin [3 ]
Zheng, Yuanyuan [1 ]
Abudumijiti, Huerxidan [1 ]
Chen, Rongxia [1 ]
Lu, Jie [1 ]
Zhou, Yingqun [1 ]
Guo, Chuanyong [1 ]
机构
[1] Tongji Univ, Sch Med, Shanghai Peoples Hosp 10, Dept Gastroenterol, Shanghai 200072, Peoples R China
[2] Nanjing Med Univ, Clin Med Coll 1, Tongji Univ, Dept Gastroenterol,Shanghai Peoples Hosp 10,Sch M, Nanjing, Jiangsu, Peoples R China
[3] Soochow Univ, Affiliated Hosp 1, Tongji Univ, Dept Gastroenterol,Shanghai Peoples Hosp 10,Sch M, Suzhou, Peoples R China
基金
中国国家自然科学基金;
关键词
15-deoxy-Delta(12,14)-prostaglandin J(2); hepatoma cell; ROS; apoptosis; JNK; ACTIVATED RECEPTOR-GAMMA; CANCER-CELLS; AKT; PATHWAY; TARGET; GROWTH; ROS; MECHANISMS; EXPRESSION; MIGRATION;
D O I
10.2147/OTT.S92832
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Objective: 15-Deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) induces reactive oxygen species (ROS)-mediated apoptosis in many malignant cells, which has not been studied in hepatoma cells. In this study, we investigated whether 15d-PGJ(2) induced apoptosis in hepatocellular carcinoma (HCC) associated with ROS. Materials and methods: The LM3, SMMC-7721, and Huh-7 HCC cell lines were treated with 15d-PGJ(2) (5-40 mu M) for 24, 48, and 72 hours. Cholecystokinin 8 was used to detect the cytotoxicity of 15d-PGJ(2). Flow cytometry, Hoechst staining, and Western blotting were used to analyze apoptosis. ROS were combined with the fluorescent probe dihydroethidium and then observed by fluorescence microscopy and flow cytometry. Activation of JNK and expression of Akt were detected by Western blotting. Results: 15d-PGJ(2) inhibited HCC cell proliferation and induced apoptosis in a dose-and time-dependent manner. Apoptosis was mainly induced via an intrinsic pathway and was ROS-dependent, and was alleviated by ROS scavengers. ROS induced JNK activation and Akt downregulation in HCC cells. Conclusion: 15d-PGJ(2) induced ROS in HCC cell lines, and inhibition of cell growth and apoptosis were partly ROS-dependent.
引用
收藏
页码:3585 / 3593
页数:9
相关论文
共 37 条
[1]   Ten years of protein kinase B signalling: a hard Akt to follow [J].
Brazil, DP ;
Hemmings, BA .
TRENDS IN BIOCHEMICAL SCIENCES, 2001, 26 (11) :657-664
[2]   Activation of PPARγ leads to inhibition of anchorage-independent growth of human colorectal cancer cells [J].
Brockman, JA ;
Gupta, RA ;
DuBois, RN .
GASTROENTEROLOGY, 1998, 115 (05) :1049-1055
[3]   15-Deoxy-γ12,14-prostaglandin J2 Reduces Liver Impairment in a Model of ConA-Induced Acute Hepatic Inflammation by Activation of PPARγ and Reduction in NF-κB Activity [J].
Chen, Kan ;
Li, Jingjing ;
Wang, Junshan ;
Xia, Yujing ;
Dai, Weiqi ;
Wang, Fan ;
Shen, Miao ;
Cheng, Ping ;
Zhang, Yan ;
Wang, Chengfen ;
Yang, Jing ;
Zhu, Rong ;
Zhang, Huawei ;
Zheng, Yuanyuan ;
Lu, Jie ;
Fan, Zhuoyi ;
Zhou, Yingqun ;
Guo, Chuanyong .
PPAR RESEARCH, 2014, 2014
[4]   Ethyl pyruvate inhibits proliferation and induces apoptosis of hepatocellular carcinoma via regulation of the HMGB1-RAGE and AKT pathways [J].
Cheng, Ping ;
Dai, Weiqi ;
Wang, Fan ;
Lu, Jie ;
Shen, Miao ;
Chen, Kan ;
Li, Jingjing ;
Zhang, Yan ;
Wang, Chengfen ;
Yang, Jing ;
Zhu, Rong ;
Zhang, Huawei ;
Zheng, Yuanyuan ;
Guo, Chuan-Yong ;
Xu, Ling .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2014, 443 (04) :1162-1168
[5]   ROS as signalling molecules:: mechanisms that generate specificity in ROS homeostasis [J].
D'Autreaux, Benoit ;
Toledano, Michel B. .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2007, 8 (10) :813-824
[6]   Anti-miR-197 inhibits migration in HCC cells by targeting KAI 1/CD82 [J].
Dai, Weiqi ;
Wang, Chengfen ;
Wang, Fan ;
Wang, Yugang ;
Shen, Miao ;
Chen, Kan ;
Cheng, Ping ;
Zhang, Yan ;
Yang, Jing ;
Zhu, Rong ;
Zhang, Huawei ;
Li, Jingjing ;
Zheng, Yuanyuan ;
Lu, Jie ;
Zhou, Yingqun ;
Xu, Ling ;
Guo, Chuanyong .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2014, 446 (02) :541-548
[7]   15-deoxy-Δ12,14-prostaglandin J2, a ligand for peroxisome proliferators-activated receptor-γ, induces apoptosis in human hepatoma cells [J].
Date, M ;
Fukuchi, K ;
Morita, S ;
Takahashi, H ;
Ohura, K .
LIVER INTERNATIONAL, 2003, 23 (06) :460-466
[8]  
Davis Jr W, 1995, BIOCHEM PHARMACOL, V50, P1021
[9]   Molecular Signatures Associated with HCV-Induced Hepatocellular Carcinoma and Liver Metastasis [J].
De Giorgi, Valeria ;
Buonaguro, Luigi ;
Worschech, Andrea ;
Tornesello, Maria Lina ;
Izzo, Francesco ;
Marincola, Francesco M. ;
Wang, Ena ;
Buonaguro, Franco M. .
PLOS ONE, 2013, 8 (02)
[10]   Modulation of mammary cancer cell migration by 15-deoxy-Δ12,14-prostaglandin J2: implications for anti-metastatic therapy [J].
Diers, Anne R. ;
Dranka, Brian P. ;
Ricart, Karina C. ;
Oh, Joo Yeun ;
Johnson, Michelle S. ;
Zhou, Fen ;
Pallero, Manuel A. ;
Bodenstine, Thomas M. ;
Murphy-Ullrich, Joanne E. ;
Welch, Danny R. ;
Landar, Aimee .
BIOCHEMICAL JOURNAL, 2010, 430 :69-78