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Oligomannurarate sulfate blocks tumor growth by inhibiting NF-κB activation

  
@article{APS6652,
	author = {Jing Zhang and Yi Chen and Xian-liang Xin and Qiu-ning Li and Ming Li and Li-ping Lin and Mei-yu Geng and Jian Ding},
	title = {Oligomannurarate sulfate blocks tumor growth by inhibiting NF-κB activation},
	journal = {Acta Pharmacologica Sinica},
	volume = {31},
	number = {3},
	year = {2016},
	keywords = {},
	abstract = {Aim:  JG3, a novel marine-derived oligosaccharide, significantly inhibits angiogenesis and tumor metastasis by blocking heparanase activity. It also arrests tumor growth, an effect that is not fully explained by its anti-heparanase activity. Here we sought to identify the mechanisms underlying JG3-mediated inhibition of tumor growth.
Methods:  Heparanase expression was assessed by RT-PCR and Western blotting. NF-κB activation status was determined using immunofluorescence, Western blotting, DNA-binding and transcription-activity assays. The effect of JG3 on upstream components of the NF-κB pathway and on selected transcription factors were monitored by Western blotting. The antitumor effect of JG3 and its relation to NF-κB activation were evaluated using four different tumor xenograft models.
Results:  We found that JG3 effectively inhibited NF-κB activation independent of heparanase expression. Our results indicate that JG3 inactivated NF-κB by interfering with the activation of upstream components of the NF-κB pathway without generally affecting the nuclear translocation of transcription factors. Further,in vivo studies demonstrated that JG3 effectively arrested the growth of tumors derived from cell lines in which NF-κB was constitutively active (BEL-7402 liver carcinoma and MDA-MB-435s breast carcinoma), but did not affect the growth of tumors derived from NF-κB-negative cell lines (SGC-7901 gastric cancer and HO-8910 ovarian carcinoma).
Conclusion:  Our data indicate that NF-κB mediates the JG3-induced arrest of tumor growth. These results define a new mechanism of action of JG3 and highlight the potential for JG3 as a promising lead molecule in cancer therapy.},
	issn = {1745-7254},	url = {http://www.chinaphar.com/article/view/6652}
}