Scope:
Hydroxytyrosol (HT), a polyphenol from olives, is a potential anticancer agent. This study was designed to evaluate the anticancer activity of HT against prostate cancer cells, and the mechanism thereof.
Methods and Results:
Treatment of LNCaP and C4–2 prostate cancer cells with HT resulted in a dose-dependent inhibition of proliferation. This was in contrast to HT’s ineffectiveness against normal prostate epithelial cells RWPE1 and PWLE2, suggesting cancer cells-specific effect. HT induced G1/S cell cycle arrest, with inhibition of cyclins D1/E and cdk2/4, and induction of inhibitory p21/p27. HT also induced apoptosis, as confirmed by flow cytometry, caspase activation, PARP cleavage and BAX/Bcl-2 ratio. It inhibited the phosphorylation of Akt / STAT3, and induced cytoplasmic retention of NF-κB, which may explain its observed effects. Finally, HT inhibited AR expression and the secretion of AR-responsive prostate-specific antigen.
Conclusion:
Castration-resistant prostate cancers retain AR signaling and are often marked by activated Akt, NF-κB and STAT3 signaling. Our results establish a pleiotropic activity of HT against these oncogenic signaling pathways. Combined with its non-toxic effects against normal cells, our results support further testing of HT for prostate cancer therapy.