Eupatorium lindleyanum DC. sesquiterpene fraction F1012-2 regulates p53/NF-κB signaling pathways in human breast cancer

F1012-2, a novel sesquiterpene lactone isolated from the Chinese herbal medicine Eupatorium lindleyanum DC, exhibits an antitumor effect. In this study, we investigated the anticancer activities of F1012-2 on ten human breast cancer lines and demonstrated significantly lower IC50 values for triple-negative breast cancer (TNBC) than for non-TNBC cell lines. The transcription factors p53 and nuclear factor-?B (NF-?B) are important regulators of tumorigenesis. F1012-2 not only depleted mutant p53, but also activated wild-type p53. F1012-2 reduced the expression of phosphorylated p65 and p105 F-?B family members and coregulated p53, NF-?B members and their dependent targets. To further clarify the key role of p53, lentivirus small hairpin RNA (shRNA) infection was used to knockdown p53 in MDAMB- 231 cells. F1012-2 significantly reduced the inhibitory effect on cell proliferation and apoptosis, while the levels of p53, NF-?B family members and their dependent genes were not significantly different. F1012-2 exhibited a significant antitumor effect and reduced the expression of p53 in MDA-MB-231 xenografts. Taken together, our results show that F1012-2 exhibited an inhibitory effect on TNBC and affected the regulation of p53/NF-?B signaling pathways.