Xanthohumol targets the JNK1/2 signaling pathway in apoptosis of human nasopharyngeal carcinoma cells

被引:11
作者
Hsieh, Ming-Yu [1 ,2 ]
Hsieh, Ming-Ju [3 ,4 ,5 ]
Lo, Yu-Sheng [3 ]
Lin, Chia-Chieh [3 ]
Chuang, Yi-Ching [3 ]
Chen, Mu-Kuan [1 ]
Chou, Ming-Chih [2 ,6 ]
机构
[1] Changhua Christian Hosp, Dept Otorhinolaryngol Head & Neck Surg, 500 South Sch St,135, Changhua, Taiwan
[2] Chung Shan Med Univ, Inst Med, Taichung, Taiwan
[3] Changhua Christian Hosp, Oral Canc Res Ctr, Changhua, Taiwan
[4] Natl Chung Hsing Univ, Coll Med, Dept Postbaccalaureate Med, Taichung, Taiwan
[5] China Med Univ, Grad Inst Biomed Sci, Taichung, Taiwan
[6] Chung Shan Med Univ Hosp, Dept Surg, Div Thorac Surg, Taichung, Taiwan
关键词
apoptosis; JNK; nasopharyngeal carcinoma; xanthohumol; PHARMACOLOGICAL PROFILE; CYCLE ARREST; CANCER; GROWTH; INHIBITION; ACTIVATION; KINASE; LINE; PROLIFERATION; SUPPRESSION;
D O I
10.1002/tox.23502
中图分类号
X [环境科学、安全科学];
学科分类号
08 ; 0830 ;
摘要
Nasopharyngeal carcinoma (NPC) is one of the most aggressive malignant tumors of the head and neck. Xanthohumol (Xn) is a compound extracted in a high concentration from the hard resin of hops (Humulus lupulus L.), the basic raw material of beer. This study investigated the apoptotic effect and anticancer properties of Xn in human NPC cell lines. Our study demonstrated that at the concentration 40 mu M, Xn significantly reduced cell viability and promoted cell cycle arrest in the G2/M phase in two cell lines. The results indicated that Xn induced apoptosis in NPC cell lines through annexin V/propidium iodide staining, chromatin condensation, and apoptosis-related pathways. Xn upregulated the expression of apoptosis-related proteins, namely DR5, cleaved RIP, caspase-3, caspase-8, caspase-9, PARP, Bim, and Bak, and it downregulated the expression of Bcl-2. Xn upregulated the c-Jun N-terminal kinase (JNK) in the mitogen-activated protein kinase (MAPK), and the inhibition of JNK clearly resulted in decreasing expression of Xn-activated cleaved caspase-3 and PARP. Our research provides sufficient evidence to confirm that Xn induces the MAPK JNK pathway to promote apoptosis of NPC and is expected to become a safe and acceptable treatment option for human NPC.
引用
收藏
页码:1509 / 1520
页数:12
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