Propolis cinnamic acid derivatives induce apoptosis through both extrinsic and intrinsic apoptosis signaling pathways and modulate of miRNA expression |
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Affiliation: | 1. Department of Biophysics, College of Basic Medical Sciences, Naval Medical University (Second Military Medical University), Shanghai, China;2. Department of Assisted Reproduction, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China |
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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. |
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Keywords: | Phytochemicals Propolis cinnamic acid derivatives TNF family Apoptosis miR-143 |
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