Propolis possesses chemopreventive properties through direct anticancer and indirect immunomodulatory activities.
Tumor necrosis factor-related apoptosis-inducing
ligand (TRAIL) plays a significant role in immunosurveillance and defense against
cancer cells. TRAIL triggers apoptosis upon binding to TRAIL-R1 (DR4) and TRAIL-R2 (DR5)
death receptors expressed on
cancer cell surface. The activation of TRAIL apoptotic signaling is considered an attractive option for
cancer prevention. However, as more
tumor cells are reported to be resistant to TRAIL-mediated death, it is important to develop new strategies to overcome this resistance. The aim of this study was to investigate the chemical composition and proapoptotic mechanism of ethanolic extract of Polish
propolis (EEP-P) against
cancer cells. The identification and quantification of phenolic compounds in
propolis extract were performed using HPLC-DAD and UPLC-Q-TOF-MS methods. TRAIL-resistant LNCaP
prostate cancer cells were treated with EEP-P and TRAIL. Cytotoxicity was measured by MTT and LDH assays. Apoptosis was detected using
annexin V-FITC staining by flow cytometry and fluorescence microscopy.
Death receptors expression was analyzed using flow cytometry.
Pinobanksin,
chrysin, methoxyflavanone,
p-coumaric acid,
ferulic acid and
caffeic acid were the main phenolics found in EEP-P.
Propolis sensitized LNCaP cells through upregulation of TRAIL-R2. These results suggest that EEP-P supports TRAIL-mediated immunochemoprevention in
prostate cancer cells.