Propolis cinnamic acid derivatives induce apoptosis through both extrinsic and intrinsic apoptosis signaling pathways and modulate of miRNA expression.

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.

• Authors: Minami Kumazaki, Haruka Shinohara, Kohei Taniguchi, Nami Yamada, Shozo Ohta, Kenji Ichihara, Yukihiro Akao
• Journal: Phytomedicine : international journal of phytotherapy and phytopharmacology (Phytomedicine) 2014 Jul-Aug Vol. 21 Issue 8-9 Pg. 1070-7 ISSN: 1618-095X [Electronic] Germany
• PMID: 24854570 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier GmbH. All rights reserved.

Chemical References

• Antineoplastic Agents, Phytogenic
• Caspase Inhibitors
• Cinnamates
• Drupanin
• FASLG protein, human
• Fas Ligand Protein
• MIRN143 microRNA, human
• MicroRNAs
• Organoplatinum Compounds
• Phenylpropionates
• TNF-Related Apoptosis-Inducing Ligand
• TNFSF10 protein, human
• Trichothecenes
• Oxaliplatin
• cinnamic acid
• artepillin C
• Propolis
• baccharin
• Fluorouracil

Topics

• Antineoplastic Agents, Phytogenic (chemistry, isolation & purification, pharmacology)
• Apoptosis (drug effects)
• Caspase Inhibitors (pharmacology)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Cinnamates (chemistry, isolation & purification, pharmacology)
• Colonic Neoplasms (drug therapy)
• Drug Synergism
• Fas Ligand Protein (genetics)
• Female
• Fluorouracil (pharmacology)
• Gene Expression Regulation, Neoplastic
• Humans
• Medicine, Traditional
• MicroRNAs (genetics)
• Models, Biological
• Organoplatinum Compounds (pharmacology)
• Oxaliplatin
• Phenylpropionates (chemistry, isolation & purification, pharmacology)
• Propolis (analogs & derivatives, chemistry, isolation & purification, pharmacology)
• Signal Transduction (drug effects)
• TNF-Related Apoptosis-Inducing Ligand (genetics)
• Trichothecenes (chemistry, isolation & purification, pharmacology)
• Up-Regulation