TY - JOUR AU - Zhang Jing AU - Chen Yi AU - Xin Xian-liang AU - Li Qiu-ning AU - Li Ming AU - Lin Li-ping AU - Geng Mei-yu AU - Ding Jian PY - 2016 TI - Oligomannurarate sulfate blocks tumor growth by inhibiting NF-κB activation JF - Acta Pharmacologica Sinica; Vol 31, No 3 (March 2010): Acta Pharmacologica Sinica Y2 - 2016 KW - N2 - 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. UR - http://www.chinaphar.com/article/view/6652