Abstract 605: Olive polyphenol, hydroxytyrosol, exerts anti-tumor effects in prostate cancer cells by targeting Akt, STAT3 and AR signaling

Abstract

Abstract Prostate cancer (PCa) is the most commonly diagnosed non-cutaneous malignancy and the second leading cause of cancer related death in men in the United States. Considering the central role of androgen-receptor (AR) signaling in PCa, surgical or medical castration [referred as androgen-deprivation therapy (ADT)] is the first line of treatment for the advanced disease. Most patients treated with ADT initially exhibit a dramatic regression of the androgen-dependent (AD) PCa cells; however, the tumors eventually progress to an androgen-independent (AI) stage. The resulting hormone-refractory tumors are highly aggressive and resistant to conventional therapies. Thus, there is an urgent need for the development of novel preventive and/or curative approaches against this advanced stage of the disease. Consumption of olive oil, which is a major component of the Mediterranean diet, has been associated with lower incidence of prostate and other malignancies. Olive oil is rich in phenolic compounds that are believed to exert beneficial effects against many pathological processes. Hydroxytyrosol (HT), an important polyphenolic constituent of virgin olive oil, has been shown to exhibit several health promoting effects such as anti-microbial, anti-atherogenic and anti-inflammatory activities. Some recent studies also suggest anti-tumor properties of HT as a consequence of its ability to induce apoptosis and inhibit the cell proliferation. In the present study, we have performed functional and biochemical assays to investigate the growth suppressive activity of HT against PCa using androgen-dependent (LNCaP) and androgen-independent (C4-2) human PCa cell lines along with normal/benign (RWPE1 and RWPE2) prostate epithelial cell lines. We observed dose- and time- dependent growth inhibitory effects of HT on both the PCa cell lines, whereas no significant effect was observed on the treated normal/benign human prostate epithelial cells. Growth inhibition in LNCaP and C4-2 cells accompanied apoptotic induction as determined by Annexin-V staining, PARP cleavage and enhanced Bax/Bcl-2 ratio. Moreover, our data demonstrated a significant decrease in the ability of HT-treated PCa cells to migrate and invade through the extra-cellular matrix. Immunoblot analyses revealed decreased phosphorylation of Akt and STAT3, two signaling proteins of pathological significance in PCa, in HT-treated PCa cells indicating their reduced activation. Importantly, we also observed a downregulated expression of AR and its downstream target gene, KLK3/PSA, in PCa cells treated with HT. These preliminary findings suggest that HT could serve as a novel nutraceutical for prevention and therapy of PCa. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 605. doi:1538-7445.AM2012-605