Mechanisms underlying isoliquiritigenin-induced apoptosis and cell cycle arrest via ROS-mediated MAPK/STAT3/NF-κB pathways in human hepatocellular carcinoma cells

被引:94
作者
Wang, Jia-Ru [1 ]
Luo, Ying-Hua [2 ]
Piao, Xian-Ji [3 ]
Zhang, Yi [1 ]
Feng, Yu-Chao [4 ]
Li, Jin-Qian [1 ]
Xu, Wan-Ting [1 ]
Zhang, Yu [1 ]
Zhang, Tong [1 ]
Wang, Shi-Nong [1 ]
Xue, Hui [1 ]
Wang, Wen-Zhong [1 ]
Cao, Long-Kui [4 ]
Jin, Cheng-Hao [1 ,4 ]
机构
[1] Heilongjiang Bayi Agr Univ, Coll Life Sci & Technol, Dept Biochem & Mol Biol, Daqing, Peoples R China
[2] Heilongjiang Bayi Agr Univ, Coll Anim Sci & Vet Med, Dept Grass Sci, Daqing, Peoples R China
[3] Harbin Med Univ, Affiliated Hosp 5, Dept Gynaecol & Obstet, Daqing, Peoples R China
[4] Heilongjiang Bayi Agr Univ, Coll Food Sci & Technol, Dept Food Sci & Engn, Daqing, Peoples R China
关键词
apoptosis; cell cycle arrest; human hepatocellular carcinoma cells; isoliquiritigenin; reactive oxygen species; NF-KAPPA-B; HYDROGEN-PEROXIDE; CANCER-CELLS; ACTIVATION; MAPK; DIFFERENTIATION; PROLIFERATION; INVOLVEMENT; INHIBITION; SUPPRESSES;
D O I
10.1002/ddr.21518
中图分类号
R914 [药物化学];
学科分类号
100705 [微生物与生化药学];
摘要
Isoliquiritigenin (ISL), a natural flavonoid isolated from plant licorice, has various pharmacological properties, including anticancer, anti-inflammatory, and antiviral effects. However, the underlying mechanisms and signaling pathways of ISL in human hepatocellular carcinoma (HCC) cells remain unknown. In this study, we evaluated the effects of ISL on the apoptosis of human HCC cells with a focus on reactive oxygen species (ROS) production. Our results showed that ISL exhibited cytotoxic effects on two human liver cancer cells in a dose-dependent manner. ISL significantly induced mitochondrial-related apoptosis and cell cycle arrest at the G2/M phase, which was accompanied by ROS accumulation in HepG2 cells. However, pretreatment with an ROS scavenger, N-acetyl-l-cysteine (NAC), inhibited ISL-induced apoptosis. In addition, ISL increased the phosphorylation levels of c-Jun N-terminal kinase (JNK), p38 kinase and inhibitor of NF-kappa B (I kappa B), and decreased the phosphorylation levels of extracellular signal-regulated kinase (ERK), signal transducer and activator of transcription 3 (STAT3), nuclear factor-kappa B (NF-kappa B), these effects were blocked by NAC and mitogen-activated protein kinase (MAPK) inhibitors. Taken together, the findings of this study indicate that ISL induced HepG2 cell apoptosis via ROS-mediated MAPK, STAT3, and NF-kappa B signaling pathways. Therefore, ISL may be a potential treatment for human HCC, as well as other cancer types.
引用
收藏
页码:461 / 470
页数:10
相关论文
共 38 条
[1]
Anti-Inflammatory and Gastroprotective Roles of Rabdosia inflexa through Downregulation of Pro-Inflammatory Cytokines and MAPK/NF-κB Signaling Pathways [J].
Akanda, Md Rashedunnabi ;
Kim, In-Shik ;
Ahn, Dongchoon ;
Tae, Hyun-Jin ;
Nam, Hyeon-Hwa ;
Choo, Byung-Kil ;
Kim, Kyunghwa ;
Park, Byung-Yong .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2018, 19 (02)
[3]
[Anonymous], J DERMATOL TREA 0406
[4]
Reactive oxygen species induce apoptosis in bronchial epithelial BEAS-2B cells by inhibiting the antiglycation glyoxalase I defence: involvement of superoxide anion, hydrogen peroxide and NF-κB [J].
Antognelli, Cinzia ;
Gambelunghe, Angela ;
Talesa, Vincenzo Nicola ;
Muzi, Giacomo .
APOPTOSIS, 2014, 19 (01) :102-116
[5]
Mitochondria and Reactive Oxygen Species: Physiology and Pathophysiology [J].
Bolisetty, Subhashini ;
Jaimes, Edgar A. .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2013, 14 (03) :6306-6344
[6]
Isoliquiritigenin Suppresses Osteosarcoma U2OS Cell Proliferation and Invasion by Regulating the PI3K/Akt Signalling Pathway [J].
Chen, Jing ;
Liu, Cheng ;
Yang, Qin-Qing ;
Ma, Rui-Bin ;
Ke, Ying ;
Dong, Fang ;
Wu, Xiao-E .
CHEMOTHERAPY, 2018, 63 (03) :155-161
[7]
Differentiation-inducing and anti-proliferative activities of isoliquiritigenin and all-trans-retinoic acid on B16F0 melanoma cells: Mechanisms profiling by RNA-seq [J].
Chen, Xiaoyu ;
Yang, Ming ;
Hao, Wenjin ;
Han, Jichun ;
Ma, Jun ;
Wang, Caixia ;
Sun, Shiguo ;
Zheng, Qiusheng .
GENE, 2016, 592 (01) :86-98
[8]
A new xanthatin analogue 1β-hydroxyl-5α-chloro-8-epi-xanthatin induces apoptosis through ROS-mediated ERK/p38 MAPK activation and JAK2/STAT3 inhibition in human hepatocellular carcinoma [J].
Fang, Xin-Yi ;
Zhang, Hai ;
Zhao, Lin ;
Tan, Shuai ;
Ren, Qing-Cuo ;
Wang, Lun ;
Shen, Xiao-Fei .
BIOCHIMIE, 2018, 152 :43-52
[9]
Identification of Michael Acceptor-Centric Pharmacophores with Substituents That Yield Strong Thioredoxin Reductase Inhibitory Character Correlated to Antiproliferative Activity [J].
Gan, Fei-Fei ;
Kaminska, Kamila K. ;
Yang, Hong ;
Liew, Chin-Yee ;
Leow, Pay-Chin ;
So, Choon-Leng ;
Tu, Lan N. L. ;
Roy, Amrita ;
Yap, Chun-Wei ;
Kang, Tse-Siang ;
Chui, Wai-Keung ;
Chew, Eng-Hui .
ANTIOXIDANTS & REDOX SIGNALING, 2013, 19 (11) :1149-1165
[10]
Goldar Samira, 2015, Asian Pac J Cancer Prev, V16, P2129