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Caffeic acid phenethylester increases stress resistance and enhances lifespan in Caenorhabditis elegans by modulation of the insulin-like DAF-16 signalling pathway.
PLoS One 2014; 9(6):e100256Plos

Abstract

CAPE is an active constituent of propolis which is widely used in traditional medicine. This hydroxycinnamic acid derivate is a known activator of the redox-active Nrf2 signalling pathway in mammalian cells. We used C. elegans to investigate the effects of this compound on accumulation of reactive oxygen species and the modulation of the pivotal redox-active pathways SKN-1 and DAF-16 (homologues of Nrf2 and FoxO, respectively) in this model organism; these results were compared to the effects in Hct116 human colon carcinoma cells. CAPE exerts a strong antioxidative effect in C. elegans: The increase of reactive oxygen species induced by thermal stress was diminished by about 50%. CAPE caused a nuclear translocation of DAF-16, but not SKN-1. CAPE increased stress resistance of the nematode against thermal stress and finally a prolongation of the median and maximum lifespan by 9 and 17%, respectively. This increase in stress resistance and lifespan was dependent on DAF-16 as shown in experiments using a DAF-16 loss of function mutant strain. Life prolongation was retained under SKN-1 RNAi conditions showing that the effect is SKN-1 independent. The results of CAPE obtained in C. elegans differed from the results obtained in Hct116 colon carcinoma cells: CAPE also caused strong antioxidative effects in the mammalian cells, but no activation of the FoxO4 signalling pathway was detectable. Instead, an activation of the Nrf2 signalling pathway was shown by luciferase assay and western blots.

CONCLUSION

CAPE activates the insulin-like DAF-16, but not the SKN-1 signalling pathway in C. elegans and therefore enhances the stress resistance and lifespan of this organism. Since modulation of the DAF-16 pathway was found to be a pivotal effect of CAPE in C. elegans, this has to be taken into account for the investigation of the molecular mechanisms of the traditional use of propolis.

Authors+Show Affiliations

Institute of Toxicology, Heinrich-Heine-Universität, Düsseldorf, Germany; Institute of Food Chemistry, Westfälische Wilhelms-Universität, Münster, Germany; Institute of Agricultural and Nutritional Sciences, Martin-Luther-Universität Halle-Wittenberg, Halle/Saale, Germany.Institute of Toxicology, Heinrich-Heine-Universität, Düsseldorf, Germany.Institute of Food Chemistry, Westfälische Wilhelms-Universität, Münster, Germany.Institute of Toxicology, Heinrich-Heine-Universität, Düsseldorf, Germany; Institute of Agricultural and Nutritional Sciences, Martin-Luther-Universität Halle-Wittenberg, Halle/Saale, Germany.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24964141

Citation

Havermann, Susannah, et al. "Caffeic Acid Phenethylester Increases Stress Resistance and Enhances Lifespan in Caenorhabditis Elegans By Modulation of the Insulin-like DAF-16 Signalling Pathway." PloS One, vol. 9, no. 6, 2014, pp. e100256.
Havermann S, Chovolou Y, Humpf HU, et al. Caffeic acid phenethylester increases stress resistance and enhances lifespan in Caenorhabditis elegans by modulation of the insulin-like DAF-16 signalling pathway. PLoS ONE. 2014;9(6):e100256.
Havermann, S., Chovolou, Y., Humpf, H. U., & Wätjen, W. (2014). Caffeic acid phenethylester increases stress resistance and enhances lifespan in Caenorhabditis elegans by modulation of the insulin-like DAF-16 signalling pathway. PloS One, 9(6), pp. e100256. doi:10.1371/journal.pone.0100256.
Havermann S, et al. Caffeic Acid Phenethylester Increases Stress Resistance and Enhances Lifespan in Caenorhabditis Elegans By Modulation of the Insulin-like DAF-16 Signalling Pathway. PLoS ONE. 2014;9(6):e100256. PubMed PMID: 24964141.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Caffeic acid phenethylester increases stress resistance and enhances lifespan in Caenorhabditis elegans by modulation of the insulin-like DAF-16 signalling pathway. AU - Havermann,Susannah, AU - Chovolou,Yvonni, AU - Humpf,Hans-Ulrich, AU - Wätjen,Wim, Y1 - 2014/06/25/ PY - 2013/09/29/received PY - 2014/05/25/accepted PY - 2014/6/26/entrez PY - 2014/6/26/pubmed PY - 2015/2/11/medline SP - e100256 EP - e100256 JF - PloS one JO - PLoS ONE VL - 9 IS - 6 N2 - UNLABELLED: CAPE is an active constituent of propolis which is widely used in traditional medicine. This hydroxycinnamic acid derivate is a known activator of the redox-active Nrf2 signalling pathway in mammalian cells. We used C. elegans to investigate the effects of this compound on accumulation of reactive oxygen species and the modulation of the pivotal redox-active pathways SKN-1 and DAF-16 (homologues of Nrf2 and FoxO, respectively) in this model organism; these results were compared to the effects in Hct116 human colon carcinoma cells. CAPE exerts a strong antioxidative effect in C. elegans: The increase of reactive oxygen species induced by thermal stress was diminished by about 50%. CAPE caused a nuclear translocation of DAF-16, but not SKN-1. CAPE increased stress resistance of the nematode against thermal stress and finally a prolongation of the median and maximum lifespan by 9 and 17%, respectively. This increase in stress resistance and lifespan was dependent on DAF-16 as shown in experiments using a DAF-16 loss of function mutant strain. Life prolongation was retained under SKN-1 RNAi conditions showing that the effect is SKN-1 independent. The results of CAPE obtained in C. elegans differed from the results obtained in Hct116 colon carcinoma cells: CAPE also caused strong antioxidative effects in the mammalian cells, but no activation of the FoxO4 signalling pathway was detectable. Instead, an activation of the Nrf2 signalling pathway was shown by luciferase assay and western blots. CONCLUSION: CAPE activates the insulin-like DAF-16, but not the SKN-1 signalling pathway in C. elegans and therefore enhances the stress resistance and lifespan of this organism. Since modulation of the DAF-16 pathway was found to be a pivotal effect of CAPE in C. elegans, this has to be taken into account for the investigation of the molecular mechanisms of the traditional use of propolis. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/24964141/Caffeic_acid_phenethylester_increases_stress_resistance_and_enhances_lifespan_in_Caenorhabditis_elegans_by_modulation_of_the_insulin_like_DAF_16_signalling_pathway_ L2 - http://dx.plos.org/10.1371/journal.pone.0100256 DB - PRIME DP - Unbound Medicine ER -