The phenolic component Oleuropein (OLEU), a bioactive natural product, has recently shown antiproliferative properties. Doxorubicin (DXR) is an anthracycline present in many chemotherapeutic schemes, although limited due to its cardio-toxic effects. Important research effort has been devoted therefore, to reducing DXR toxicity without compromising its antitumor efficacy. The anticancer actions of DXR and OLEU were assessed, on PC-3 prostate cancer cells, while cell cycle distribution and rate of apoptosis were assessed by flow cytometry. The autophagic process was determined via immunoblotting and immunofluorescent staining. Finally, cell extracts were analyzed by NMR spectroscopy. The present study showed that both DXR and OLEU inhibited PC-3 cells proliferation, while the co-treatment with DXR and OLEU resulted in an additive inhibition. Although the addition of OLEU to DXR did not alter significantly the cell cycle distribution, exhibited by each treatment alone, and produced a marginal increase on the rate of apoptosis, both compounds produced a remarkable induction of autophagy. In addition, treated cells exhibited significant metabolite alterations. This study demonstrates that OLEU, a basic component of the everyday diet, is capable of lowering significantly the cytotoxic dose of DXR, while obtaining an important anti-proliferative effect in prostate cancer cells.

Experimental and epidemiological studies have shown that antioxidant polyphenols can act as chemopreventive agents against prostate cancer. Cabernet Sauvignon and Rombola wine were extracted in order to obtain fractions containing different classes of compounds. All extracts inhibited the androgen-insensitive human prostate cancer cells (PC-3) proliferation in a dose-dependent manner. The most potent compounds were selected to be further tested.Treatment of PC-3 cells with the selected wine extracts marginally increased the cell distribution in S phase, while producing a remarkable induction of autophagy. Finally, the levels of glutathione along with the concentration of hydrogen peroxide and nitrogen oxide were modulated in the treated cells. Herein, we show that red and wine extracts have direct effects on the proliferation, survival, oxidative status, and the induction of autophagy of PC-3 cells. Our data may have important implications for the design of a more effective adjuvant treatment for prostate cancer patients.

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