The role of Nrf2 and apoptotic signaling pathways in oroxylin A-mediated responses in HCT-116 colorectal adenocarcinoma cells and xenograft tumors

被引:27
作者
Hu, Rong [1 ]
Chen, Nan [1 ]
Yao, Jing [1 ]
Zhao, Qing [1 ]
Zhang, Fengyi [1 ]
Li, Zhi-Yu [1 ]
You, Qi-Dong [1 ]
Guo, Qing-Long [1 ]
机构
[1] China Pharmaceut Univ, Dept Physiol, State Key Lab Nat Med, Jiangsu Key Lab Carcinogenesis & Intervent, Nanjing 210009, Peoples R China
基金
中国国家自然科学基金;
关键词
apoptosis; chemoprevention; Nrf2; oroxylin A; GENE-EXPRESSION; SCUTELLARIA-BAICALENSIS; IN-VITRO; CANCER-PREVENTION; GROWTH; CHEMOPREVENTION; INDUCTION; ACTIVATION; (-)-EPIGALLOCATECHIN-3-GALLATE; GLUTATHIONE;
D O I
10.1097/CAD.0b013e3283512703
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Oroxylin A is a flavonoid found in the roots of Scutellaria baicalensis Georgi, a herbal medicine commonly used as an antipyretic, analgesic, antitumor, and anti-inflammatory agent. It has recently been investigated for its anticancer activities in hepatoma, gastric, and breast tumors. Here, we investigated the antitumor effects of oroxylin A in human colon carcinoma HCT-116 cells in vitro and in vivo. We characterized the proapoptotic effect of oroxylin A using diamidino-phenyl-indole (DAPI) and annexin V/PI staining. We then found that both caspase-3 and caspase-9 were activated, the expression of Bcl-2 protein decreased, and the expression of Bax protein increased after treatment with oroxylin A. In addition, oroxylin A increased nuclear transcription factor erythroid-related factor 2 (Nrf2) expression and induced Nrf2 translocation into the nucleus. Furthermore, we found that oroxylin A treatment elevated intracellular reactive oxygen species levels and increased the protein expression level of two of the Nrf2 target genes heme oxygenase-1 and NADP(H): quinone oxidoreductase-1 in HCT-116 cells. Finally, our study demonstrated that oral administration of oroxylin A significantly decreased tumor volume and weight in immunodeficient mice that were inoculated with HCT-116 cells. The in-vivo chemopreventive efficacy of oroxylin A against HCT-116 human colon cancer was accompanied by its proapoptotic and Nrf2-inducing activities, which correlates with the in-vitro study. This is the first demonstration of oroxylin A-dependent chemoprevention in colon cancer and may offer a potential mechanism for its anticancer action in vivo. Anti-Cancer Drugs 23:651-658 (C) 2012 Wolters Kluwer Health broken vertical bar Lippincott Williams & Wilkins.
引用
收藏
页码:651 / 658
页数:8
相关论文
共 36 条
[1]   Enhanced Anti-tumor Activity by the Combination of the Natural Compounds (-)-Epigallocatechin-3-gallate and Luteolin POTENTIAL ROLE OF p53 [J].
Amin, A. R. M. Ruhul ;
Wang, Dongsheng ;
Zhang, Hongzheng ;
Peng, Shifang ;
Shin, Hyung Ju C. ;
Brandes, Johann C. ;
Tighiouart, Mourad ;
Khuri, Fadlo R. ;
Chen, Zhuo Georgia ;
Shin, Dong M. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2010, 285 (45) :34557-34565
[2]   Curcurnin activates the haem oxygenase-1 gene via regulation of Nrf2 and the antioxidant-responsive element [J].
Balogun, E ;
Hoque, M ;
Gong, PF ;
Killeen, E ;
Green, CJ ;
Foresti, R ;
Alam, J ;
Motterlini, R .
BIOCHEMICAL JOURNAL, 2003, 371 :887-895
[3]   Characterization of chemical constituents in Scutellaria baicalensis with antiandrogenic and growth-inhibitory activities toward prostate carcinoma [J].
Bonham, M ;
Posakony, J ;
Coleman, I ;
Montgomery, B ;
Simon, J ;
Nelson, PS .
CLINICAL CANCER RESEARCH, 2005, 11 (10) :3905-3914
[4]   Epigallocatechin-3-gallate-induced stress signals in HT-29 human colon adenocarcinoma cells [J].
Chen, C ;
Shen, GX ;
Hebbar, V ;
Hu, R ;
Owuor, ED ;
Kong, ANT .
CARCINOGENESIS, 2003, 24 (08) :1369-1378
[5]   Oroxylin A inhibition of lipopolysaccharide-induced iNOS and COX 2 gene expression via suppression of nuclear factor-κB activation [J].
Chen, YC ;
Yang, LL ;
Lee, TJF .
BIOCHEMICAL PHARMACOLOGY, 2000, 59 (11) :1445-1457
[6]   Wogonin sensitizes resistant malignant cells to TNFα- and TRAIL-induced apoptosis [J].
Fas, Stefanie C. ;
Baumann, Sven ;
Zhu, Jia Yun ;
Giaisi, Marco ;
Treiber, Monika K. ;
Mahlknecht, Ulrich ;
Krammer, Peter H. ;
Li-Weber, Min .
BLOOD, 2006, 108 (12) :3700-3706
[7]   Activation of the Nrf2-ARE signaling pathway: a promising strategy in cancer prevention [J].
Giudice, A ;
Montella, M .
BIOESSAYS, 2006, 28 (02) :169-181
[8]   Recent advances in chemoprevention of cancer [J].
Hong, WK ;
Sporn, MB .
SCIENCE, 1997, 278 (5340) :1073-1077
[9]   The dietary flavonoid apigenin sensitizes malignant tumor cells to tumor necrosis factor-related apoptosis-inducing ligand [J].
Horinaka, M ;
Yoshida, T ;
Shiraishi, T ;
Nakata, S ;
Wakada, M ;
Sakai, T .
MOLECULAR CANCER THERAPEUTICS, 2006, 5 (04) :945-951
[10]   Preclinical Colorectal Cancer Chemopreventive Efficacy and p53-Modulating Activity of 3′,4′,5′-Trimethoxyflavonol, a Quercetin Analogue [J].
Howells, Lynne M. ;
Britton, Robert G. ;
Mazzoletti, Marco ;
Greaves, Peter ;
Broggini, Massimo ;
Brown, Karen ;
Steward, William P. ;
Gescher, Andreas J. ;
Sale, Stewart .
CANCER PREVENTION RESEARCH, 2010, 3 (08) :929-939