Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 18, Issue 8, Pages -Publisher
MDPI
DOI: 10.3390/ijms18081619
Keywords
mollugin; cancer; NF-kappa B; NF-kappa B target genes
Funding
- National Natural Science Foundation of China [81360496, 81660608]
- Jilin Province Science and Technology Development Plan item [2030101229JC]
- Education Department of Jilin Province [2016.281]
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The NF-B signaling pathway plays a pivotal role in regulating the immune response and inflammation. However, it has been shown that NF-B also has a major role in oncogenesis. Therefore, NF-B inhibitors have been considered as potential drugs against cancer. Herein, we searched for NF-B inhibitors from natural sources and identified mollugin from the roots of Rubia cordifolia L. as an inhibitor of NF-B activation. We found that mollugin significantly inhibited the expression of an NF-B reporter gene induced by tumor necrosis factor (TNF)- in a dose-dependent manner. Moreover, mollugin inhibited TNF--induced phosphorylation and nuclear translocation of p65, phosphorylation and degradation of inhibitor of B (IB), and IB kinase (IKK) phosphorylation. Furthermore, we discovered that pretreatment of cells with mollugin prevented the TNF--induced expression of NF-B target genes, such as genes related to proliferation (COX-2, Cyclin D1 and c-Myc), anti-apoptosis (Bcl-2, cIAP-1 and survivin), invasion (MMP-9 and ICAM-1), and angiogenesis (VEGF). We also demonstrated that mollugin potentiated TNF--induced apoptosis and inhibited proliferation of HeLa cells. We further demonstrated in vivo that mollugin suppressed the growth of tumor xenografts derived from HeLa cells. Taken together, mollugin may be a valuable candidate for cancer treatment by targeting NF-B.
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