Abstract
Propolis cinnamic acid derivatives have a number of biological activities including anti-oxidant and anti-cancer ones. In this study, we aimed to elucidate the mechanism of the anti-cancer activity of 3 representative propolis cinnamic acid derivatives, i.e., Artepilin C, Baccharin and Drupanin in human colon cancer cell lines. Our study demonstrated that these compounds had a potent apoptosis-inductive effect even on drug-resistant colon cancer cells. Combination treatment of human colon cancer DLD-1 cells with 2 of these compounds, each at its IC20 concentration, induced apoptosis by stimulating both intrinsic and extrinsic apoptosis signaling pathways. Especially, Baccharin plus Drupanin exhibited a synergistic growth-inhibitory effect by strengthening both intrinsic and extrinsic apoptotic signaling transduction through TRAIL/DR4/5 and/or FasL/Fas death-signaling loops and by increasing the expression level of miR-143, resulting in decreased expression levels of the target gene MAPK/Erk5 and its downstream target c-Myc. These data suggest that the supplemental intake of these compounds found in propolis has enormous significance with respect to cancer prevention.
Keywords:
Apoptosis; Phytochemicals; Propolis cinnamic acid derivatives; TNF family; miR-143.
Copyright © 2014 Elsevier GmbH. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents, Phytogenic / chemistry
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Antineoplastic Agents, Phytogenic / isolation & purification
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Antineoplastic Agents, Phytogenic / pharmacology*
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Apoptosis / drug effects
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Caspase Inhibitors / pharmacology
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Cell Line, Tumor
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Cell Survival / drug effects
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Cinnamates / chemistry
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Cinnamates / isolation & purification
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Cinnamates / pharmacology*
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Colonic Neoplasms / drug therapy*
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Drug Synergism
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Fas Ligand Protein / genetics
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Female
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Fluorouracil / pharmacology
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Gene Expression Regulation, Neoplastic*
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Humans
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Medicine, Traditional
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MicroRNAs / genetics*
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Models, Biological
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Organoplatinum Compounds / pharmacology
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Oxaliplatin
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Phenylpropionates / chemistry
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Phenylpropionates / isolation & purification
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Phenylpropionates / pharmacology
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Propolis / analogs & derivatives
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Propolis / chemistry
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Propolis / isolation & purification
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Propolis / pharmacology*
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Signal Transduction / drug effects
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TNF-Related Apoptosis-Inducing Ligand / genetics
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Trichothecenes / chemistry
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Trichothecenes / isolation & purification
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Trichothecenes / pharmacology
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Up-Regulation
Substances
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Antineoplastic Agents, Phytogenic
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Caspase Inhibitors
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Cinnamates
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Drupanin
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FASLG protein, human
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Fas Ligand Protein
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MIRN143 microRNA, human
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MicroRNAs
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Organoplatinum Compounds
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Phenylpropionates
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TNF-Related Apoptosis-Inducing Ligand
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TNFSF10 protein, human
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Trichothecenes
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Oxaliplatin
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cinnamic acid
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artepillin C
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Propolis
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baccharin
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Fluorouracil