Mollugin Has an Anti-Cancer Therapeutic Effect by Inhibiting TNF-α-Induced NF-κB Activation

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.