The preventive effects of hyperoside on lung cancer in vitro by inducing apoptosis and inhibiting proliferation through Caspase-3 and P53 signaling pathway

被引:54
作者
Liu, Yuan-hua [1 ]
Liu, Guang-hui [2 ]
Mei, Jing-jing [1 ]
Wang, Jing [1 ]
机构
[1] Zhengzhou Univ, Affiliated Hosp 1, Dept Resp & Crit Care Med, JianShe Rd, Zhengzhou 450052, Peoples R China
[2] Zhengzhou Univ, Affiliated Hosp 1, Dept Gastrointestinal Surg, JianShe Rd, Zhengzhou 450052, Peoples R China
关键词
Lung cancer; Hyperoside; Apoptosis; Proliferation; NF-KAPPA-B; CELL-CYCLE ARREST; AUTOPHAGY; ACID; INFLAMMATION; COMBINATION; ASSOCIATION; METASTASIS; EXPRESSION; QUERCETIN;
D O I
10.1016/j.biopha.2016.06.035
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Though advanced surgical operation and chemotherapy have been under taken, lung cancer remains one of the most aggressive and fatal human malignancies with a low survival rate. Thus, novel therapeutic strategies for prevention and remedy are urgently needed in lung cancer. Hyperoside, known as quercetin-3-O-beta-D-galactopyranoside, is a natural flavonol glycoside discovered in plants of genera Hypericum, displaying anti-oxidant, anticancer, and anti-inflammatory properties. In the study, we attempted to investigate whether hyperoside could inhibit lung cancer progression via Caspase-3- and P53-regulated cell death. In in vitro and in vivo experiments, we explored hyperoside at three different dosages on cell apoptosis, cell proliferation, cell migration, cell invasion, cell cycle distribution, the related signalling pathways, as well as xenograft tumor growth. Our data suggested that hyperoside exerted inhibitory role in lung cancer development. Inhibition of NF-kappa B transcriptional activity, Caspase9/Caspase-3 activation, the cell cycle arrest, and suppression of cell proliferation-related signaling pathway led to the lung cancer inhibition. Further, via mice xenograft model in vivo, we indicated that hyperoside completely impeded tumor growth through angiogenesis inhibition. Our study illustrated that hyperoside might provide a synergistic anticancer effects that warrant further study and investigation due to its potential role in clinical applications. (C) 2016 Elsevier Masson SAS. All rights reserved.
引用
收藏
页码:381 / 391
页数:11
相关论文
共 42 条
[1]   Autophagy delays apoptotic death in breast cancer cells following DNA damage [J].
Abedin, M. J. ;
Wang, D. ;
McDonnell, M. A. ;
Lehmann, U. ;
Kelekar, A. .
CELL DEATH AND DIFFERENTIATION, 2007, 14 (03) :500-510
[2]   RETRACTED: A cell cycle regulatory network controlling NF-κB subunit activity and function (Retracted article. See vol. 33, pg. 1978, 2014) [J].
Barre, Benjamin ;
Perkins, Neil D. .
EMBO JOURNAL, 2007, 26 (23) :4841-4855
[3]   The inhibition of PI3K and NFκB promoted curcumin-induced cell cycle arrest at G2/M via altering polyamine metabolism in Bcl-2 overexpressing MCF-7 breast cancer cells [J].
Berrak, Ozge ;
Akkoc, Yunus ;
Arisan, Elif Damla ;
Coker-Gurkan, Ajda ;
Obakan-Yerlikaya, Pinar ;
Palavan-Unsal, Narcin .
BIOMEDICINE & PHARMACOTHERAPY, 2016, 77 :150-160
[4]   The E3 ubiquitin ligase itch couples JNK activation to TNFα-induced cell death by inducing c-FLIPL turnover [J].
Chang, LF ;
Kamata, H ;
Solinas, G ;
Luo, JL ;
Maeda, S ;
Venuprasad, K ;
Liu, YC ;
Karin, M .
CELL, 2006, 124 (03) :601-613
[5]   Involvement of PI3K/PTEN/AKT/mTOR pathway in invasion and metastasis in hepatocellular carcinoma: Association with MMP-9 [J].
Chen, Jing-song ;
Wang, Qian ;
Fu, Xin-hui ;
Huang, Xiao-Hui ;
Chen, Xi-lin ;
Cao, Liang-qi ;
Chen, Lian-zhou ;
Tan, Hao-xiang ;
Li, Wen ;
Bi, Jiong ;
Zhang, Long-juan .
HEPATOLOGY RESEARCH, 2009, 39 (02) :177-186
[6]   Annual report on status of cancer in China, 2010 [J].
Chen, Wanqing ;
Zheng, Rongshou ;
Zhang, Siwei ;
Zhao, Ping ;
Zeng, Hongmei ;
Zou, Xiaonong ;
He, Jie .
CHINESE JOURNAL OF CANCER RESEARCH, 2014, 26 (01) :48-58
[7]   Antimetastatic potential of fisetin involves inactivation of the PI3K/Akt and JNK signaling pathways with downregulation of MMP-2/9 expressions in prostate cancer PC-3 cells [J].
Chien, Chi-Sheng ;
Shen, Kun-Hung ;
Huang, Jau-Shyang ;
Ko, Shian-Chin ;
Shih, Yuan-Wei .
MOLECULAR AND CELLULAR BIOCHEMISTRY, 2010, 333 (1-2) :169-180
[8]   Adenovirus-mediated bcl-2 gene transfer inhibits renal ischemia/reperfusion induced tubular oxidative stress and apoptosis [J].
Chien, CT ;
Chang, TC ;
Tsai, CY ;
Shyue, SK ;
Lai, MK .
AMERICAN JOURNAL OF TRANSPLANTATION, 2005, 5 (06) :1194-1203
[9]   Zinc deficiency-induced cell death [J].
Clegg, MS ;
Hanna, LA ;
Niles, BJ ;
Momma, TY ;
Keen, CL .
IUBMB LIFE, 2005, 57 (10) :661-669
[10]   Akt-dependent regulation of NF-κB is controlled by mTOR and Raptor in association with IKK [J].
Dan, Han C. ;
Cooper, Matthew J. ;
Cogswell, Patricia C. ;
Duncan, Joseph A. ;
Ting, Jenny P. -Y. ;
Baldwin, Albert S. .
GENES & DEVELOPMENT, 2008, 22 (11) :1490-1500