Ethanolic Extract of Polish Propolis: Chemical Composition and TRAIL-R2 Death Receptor Targeting Apoptotic Activity against Prostate Cancer Cells

Abstract

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.

Phenolic Profile and Antioxidant Activity of Propolis Extracts From Poland

“…All the examined acids were previously identified in propolis samples collected from Poland and other European countries, for example Greece, Slovenia, or Italy. 2,14,16,17,19,30 The chemical composition of Polish propolis extracts prepared in 70% and 96% ethanol suggests that aqueous ethanol is a better solvent for extraction of phenolic compounds, especially flavonoids from raw propolis, which was confirmed by statistical analysis. Mavri et al 2 stated that propolis extract obtained using 70% ethanol as the extraction solvent contained higher amounts of flavonoids and phenolic acids than the propolis extract prepared by extracting the material with 96% ethanol.…”

“…28,29 High concentrations, especially in EEP70, were also recorded for galangin, chrysin, apigenin, and kaempferol, previously reported in propolis samples collected from various regions of Poland. 14,16,19,30 The concentration of apigenin and kaempferol in both examined extracts was higher than in propolis extracts from Italy, Spain, and China. 28,29 The concentration of chrysin in Italian propolis extracts (4.38-4.56 mg/mL) was higher than in EEP96 and comparable to concentration in EEP70.…”

“…7 Among all the groups of chemical compounds, phenols (flavonoids, phenolic acids, and their esters) are regularly determined in propolis samples collected from different sources and are major bioactive constituents of this material. 1,[13][14][15][16][17][18][19][20][21][22][23] Phenols possess biological properties including ability in scavenging reactive oxygen species, which are responsible for majority of the diseases, such as various types of cancer, diabetes, or cardiovascular diseases. 24,25 The chemical composition and biological activities of propolis have been determined in its extracts obtained using diverse solvents, including methanol, acetone, chloroform, or ethanol in different concentrations.…”

Inhibitory effect of snake venom toxin on NF-κB activity prevents human cervical cancer cell growth via increase of death receptor 3 and 5 expression

“…Activation of death receptors (DRs) such as tumor necrosis factor receptor 1 (TNFR1), FAS (TNFRSF6) and the TNF-related apoptosis-inducing ligand (TRAIL) receptors, TRAIL-R1 (DR4) and TRAIL-R2 (DR5) is important for anticancer effects of chemotherapeutics Szliszka et al 2013). An activated DR triggers activation of caspases, including caspases-3, 8 and-9, as well as the increase of Bax and decrease of Bcl-2 (Kantari and Walczak 2011;Kaufmann et al 2012;Yin 2000).…”

The Ethanol Extract of Polish Propolis Exhibits Anti-Proliferative and/or Pro-Apoptotic Effect on HCT 116 Colon Cancer and Me45 Malignant Melanoma Cells In Vitro Conditions.

“…The vast majority of studies demonstrated that propolis reveals substantial properties, including the promotion of soft tissues healing and regeneration/reparation. Apart from its antibacterial [1][2][3][4][5][6], anti-inflammatory [7,8], antioxidant [9][10][11], immunoprotective [12], hepatoprotective activities [13,14], propolis has also anti-proliferative [15][16][17][18][19] and proapoptotic ones [20][21][22][23]. Composition of propolis is diverse and depends on both place of origin and time in which it has been collected.…”