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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.
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页码:651 / 658
页数:8
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