Abstract. the nuclear factor κB (NF-κB)/inhibitor of κ kinase-β (IKKβ) signaling pathway is important in tumor promotion and progression. MDA-MB-231 human breast carcinoma cells express COX-2 and show a constitutive phosphorylation of NF-κB. Many non-specific inhibitors of IKKβ and NF-κB are used to inhibit tumor promotion and progression. the Stephania delavayi Diels. (S. delavayi Diels.) extract has been reported to safely activate B cell immunity and there is evidence suggesting that it may be a promising new anticancer therapeutic agent. S. delavayi Diels. extract suppressed proliferation of the breast cancer cell lines MDA-MB-231 and MCF-7 by inducing cell death. to aid in the development of the S. delavayi Diels. extract as a therapeutic agent, its mechanisms of action were investigated, in particular its effects on p38 MApK, NF-κB and COX-2, which play important roles in inflammation and cancer. S. delavayi Diels. stimulated p38 MApK phosphorylation but reduced NF-κB phosphorylation and COX-2 expression in a dose-and timedependent manner. thus, S. delavayi Diels., which appears to act primarily through p38 MApK/NF-κB/COX-2 signaling in breast carcinomas, may be a potent anticancer agent with target specificity and low toxicity.

The World Health Organization (WHO) has reported that cancer is one of the most prevalent diseases and a leading cause of death worldwide. Many anticancer drug development studies have been pursued over the last few decades and several viable drugs have been discovered, such as paclitaxel, topotecan and irinotecan. Previously, our research group uncovered the cytocidal and cytostatic effects of the plant Stephania delavayi Diels. In this study, we determined the active chemical to be 6,7-di-O-acetylsinococuline (FK-3000). The FK-3000 half maximal inhibitory concentration (IC50) in MDA-MB-231 breast carcinoma cells at 48 h was 0.52 μg/ml and it induced apoptosis in a dose- and time-dependent manner. FK-3000 suppressed NF-κB nuclear translocation, decreased NF-κB phosphorylation, and decreased COX-2 protein expression. MDA-MB-231 xenografted mice were treated with FK-3000, Taxol, or their combination for 21 days. The tumor size was smallest in the co-treatment group, indicating that FK-3000 may have a synergistic effect with Taxol. FK-3000 treatment showed no adverse effects on blood cell counts, serum protein levels, or pathology. These studies demonstrate that FK-3000, isolated from S. delavayi Diels., is a promising, pathway-specific anticancer agent that exhibits low toxicity.