Abstract
Ethanolic extract of propolis (EEP) is one of the richest sources of phenolic acids and flavonoids. EEP and its phenolic compounds have been known for various biological activities including immunopotentiation, chemopreventive and antitumor effects. Tumor necrosis factor related apoptosis inducing ligand (TRAIL) is a naturally occurring anticancer agent that preferentially induces apoptosis in cancer cells and is not toxic toward normal cells. We examined the cytotoxic and apoptotic effect of EEP and phenolic compounds identified in propolis in combination with TRAIL on HeLa cancer cells. HeLa cells were resistant to TRAIL-induced apoptosis. Our study demonstrated that EEP and its components significantly sensitize to TRAIL induced death in cancer cells. The percentage of the apoptotic cell after exposure to 50 μg/mL EEP and 100 ng/mL TRAIL increased to 71.10±1.16%. The strongest cytotoxic effect in combination with TRAIL on HeLa cells exhibited apigenin and CAPE at the concentration of 50 μM (58.87±0.75% and 49.59±0.39%, respectively). In this report, we show for the first time that EEP markedly augmented TRAIL mediated apoptosis in cancer cells and confirmed the importance of propolis in chemoprevention of malignant tumors.
Highlights
Cancer is one of the major public health burdens in Europe and United States of America causing approximately 7 million deaths every year worldwide
We show for the first time that Ethanolic extract of propolis (EEP) markedly augmented Tumor necrosis factor related apoptosis inducing ligand (TRAIL) mediated apoptosis in cancer cells and confirmed the importance of propolis in chemoprevention of malignant tumors
We showed for the first time that EEP sensitizes HeLa cell to TRAIL induced apoptosis
Summary
Cancer is one of the major public health burdens in Europe and United States of America causing approximately 7 million deaths every year worldwide. Epidemiological and preclinical evidence suggest that phenolic and polyphenolic phytochemicals in propolis possess cancer chemopreventive properties [3,4,9]. Several mechanisms contribute to the overall cancer preventive and antitumor effects of propolis and its phenolic components. The enhancement of host immune function by propolis may be beneficial to cancer chemoprevention. This study was designed to investigate the apoptotic and/or cytotoxic effect of EEP and some of the phenolic compounds found in our sample of propolis [13] (Figure 1) with or without TRAIL on HeLa cells. The overcome of TRAIL-resistance in tumor cells by propolis and its phenolic components may be one of the mechanisms responsible for their cancer chemopreventive effects
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