eCAM Advance Access published online on November 5, 2009
eCAM, doi:10.1093/ecam/nep180
Ethanolic Extract of Propolis Augments TRAIL-Induced Apoptotic Death in Prostate Cancer Cells
1Chair and Department of Microbiology and Immunology, Jordana 19, 41808 Zabrze and 2Chair and Department of Urology, 3-go Maja 13, 41 800 Zabrze, Medical University of Silesia in Katowice, Poland
Prostate cancer is a commonly diagnosed cancer in men. The ethanolic extract of propolis (EEP) and its phenolic compounds possess immunomodulatory, chemopreventive and antitumor effects. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/APO2L) is a naturally occurring anticancer agent that preferentially induces apoptosis in cancer cells and is not toxic to normal cells. We examined the cytotoxic and apoptotic effects of EEP and phenolic compounds isolated from propolis in combination with TRAIL on two prostate cancer cell lines, hormone-sensitivity LNCaP and hormone-refractory DU145. The cytotoxicity was evaluated by MTT and LDH assays. The apoptosis was determined using flow cytometry with annexin V-FITC/propidium iodide. The prostate cancer cell lines were proved to be resistant to TRAIL-induced apoptosis. Our study demonstrated that EEP and its components significantly sensitize to TRAIL-induced death in prostate cancer cells. The percentage of the apoptotic cells after cotreatment with 50 µg ml–1 EEP and 100 ng ml–1 TRAIL increased to 74.9 ± 0.7% for LNCaP and 57.4 ± 0.7% for DU145 cells. The strongest cytotoxic effect on LNCaP cells was exhibited by apigenin, kaempferid, galangin and caffeic acid phenylethyl ester (CAPE) in combination with TRAIL (53.51 ± 0.68 – 66.06 ± 0.62% death cells). In this work, we showed that EEP markedly augmented TRAIL-mediated apoptosis in prostate cancer cells and suggested the significant role of propolis in chemoprevention of prostate cancer.
Keywords: apoptosis – cancer chemoprevention – flavonoids – phenolic acids – propolis – tumor necrosis factor related apoptosis inducing ligand
For reprints and all correspondence: Wojciech Krol Chair and Department of Microbiology and Immunology, Jordana 19, 41 808 Zabrze, Poland. Tel/Fax: +48-32-2722554; E-mail: wkrol{at}sum.edu.pl
Received February 28, 2009; accepted October 6, 2009