Background: We identified increased β-catenin and Atk expression was associated with drug resistance and poor prognosis in breast cancer patients using public databases. Antrocin treatment suppressed breast tumorigenesis and stemness properties. Hypothesis/Purpose: We aimed to provide preclinical evidence for antrocin, an active component of Antrodia cinnamomea, as a potential small-molecule drug for treating drug-resistant breast cancer. Methods: Various in vitro assays including SRB, Boyden chamber, colony formation, drug combination index and tumor sphere generation were used to determine the anti-cancer and stemness effects of antrocin. Mouse xenograft models were used to evaluate antrocin's effect in vivo. Results: Antrocin treatment suppressed the viability, migration colony formation and mammosphere generation. Antrocin-mediated anti-cancer effects were associated with the decreased expression of oncogenic and stemness markers such as β-catenin, Akt and Notch1. A sequential regimen of antrocin and paclitaxel synergistically inhibit breast cancer viability in vitro and in vivo. Conclusion: Our preclinical evidence supports antrocin's ability of inhibiting tumorigenic and stemness properties in breast cancer cells. Further develop of antrocin should be encouraged; the combined use of antrocin and paclitaxel may also be considered for future clinical trials.
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