Tilapia (Oreochromis mossambicus) antimicrobial peptide, hepcidin 1-5, shows antitumor activity in cancer cells

被引:75
作者
Chang, Wang-Ting [2 ]
Pan, Chieh-Yu [1 ]
Rajanbabu, Venugopal [1 ]
Cheng, Chun-Wen [2 ]
Chen, Jyh-Yih [1 ]
机构
[1] Acad Sinica, Inst Cellular & Organism Biol, Marine Res Stn, Jiaushi 262, Ilan, Taiwan
[2] Chung Shan Med Univ, Inst Biochem & Biotechnol, Taichung 402, Taiwan
关键词
Antimicrobial peptide; Hepcidin; 1-5; Antitumor activity; IRON; CATHELICIDIN; EXPRESSION; MONOCYTES; CYTOKINE; RECEPTOR; LL-37;
D O I
10.1016/j.peptides.2010.11.003
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The inhibitory function of tilapia hepcidin (TH)1-5, an antimicrobial peptide, was not examined in previous studies. In this study, we synthesized the TH1-5 peptide and tested TH1-5's antitumor activity against several tumor cell lines. We show that TH1-5 inhibited the proliferation of tumor cells and reduced colony formation in a soft agar assay. Scanning electron microscopy and transmission electron microscopy showed that TH1-5 altered the membrane structure similar to the function of a lytic peptide. Acridine orange/ethidium bromide staining, a wound-healing assay, and a flow cytometric analysis showed that TH1-5 induced necrosis with high-concentration treatment and induced apoptosis with low-concentration treatment. Inflammation is known to be closely associated with the development of cancer. TH1-5 showing anti-inflammatory effects in a previous publication induced us to evaluate the anti-inflammatory effects in cancer cell lines through the expressions of immune-related genes after being treated with the TH1-5 peptide. However, real-time qualitative RT-PCR indicated that TH1-5 treatment induced downregulation of the expressions of interleukin (IL)-6, IL-8, IL-12, IL-15, interferon-gamma, CTSG, caspase-7, and Bcl-2, and upregulation of IL-2 and CAPN5 in HeLa cells, and upregulation of IL-8 and CTSG in HT1080 cells. These results suggest that TH1-5 possibly induces an inflammatory response in HeLa cells, but not in HT1080 cells. Overall, these results indicate that TH1-5 possesses the potential to be a novel peptide for cancer therapy. (C) 2010 Elsevier Inc. All rights reserved.
引用
收藏
页码:342 / 352
页数:11
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