Comprehensive Proteomic Study of the Antiproliferative Activity of a Polyphenol-Enriched Rosemary Extract on Colon Cancer Cells Using Nanoliquid Chromatography-Orbitrap MS/MS.
In this work, a proteomics strategy based on nanoliquid chromatography-tandem mass spectrometry (nano-LC-MS/MS) using an Orbitrap high-resolution mass spectrometer together with stable isotope dimethyl labeling (DML) is applied to quantitatively examine relative changes in the protein fraction of HT-29 human colon cancer cells treated with different concentrations of a polyphenol-enriched rosemary extract over the time. The major objective of this study was to gain insights into the antiproliferative mechanisms induced by rosemary polyphenols. Using this methodology, 1909 and 698 proteins were identified and quantified in cell extracts. The polyphenol-enriched rosemary extract treatment changed the expression of several proteins in a time- and concentration-dependent manner. Most of the altered proteins are implicated in the activation of Nrf2 transcription factor and the unfolded protein response. In conclusion, rosemary polyphenols induced proteomic changes that were related to the attenuation of aggresome formation and activation of autophagy to alleviate cellular stress.
Laboratory of Foodomics, Institute of Food Science Research (CIAL, CSIC) , Calle Nicolás Cabrera 9, 28049 Madrid, Spain.
Alberto
A
Valdés
Analytical Chemistry, Department of Chemistry-BMC and SciLifeLab, Uppsala University , Husargatan 3, 75124 Uppsala, Sweden.
Konstantin A
KA
Artemenko
Analytical Chemistry, Department of Chemistry-BMC and SciLifeLab, Uppsala University , Husargatan 3, 75124 Uppsala, Sweden.
Jonas
J
Bergquist
Laboratory of Foodomics, Institute of Food Science Research (CIAL, CSIC) , Calle Nicolás Cabrera 9, 28049 Madrid, Spain.
Virginia
V
García-Cañas
Laboratory of Foodomics, Institute of Food Science Research (CIAL, CSIC) , Calle Nicolás Cabrera 9, 28049 Madrid, Spain.
Alejandro
A
Cifuentes
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects; D002853:Chromatography, Liquid; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000473:pathology*; D019073:HT29 Cells; D006801:Humans; D007553:Isotope Labeling; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D059808:Polyphenols / Q000494:pharmacology; D020543:Proteome / Q000187:drug effects*; D040901:Proteomics / Q000379:methods*; D027542:Rosmarinus / Q000737:chemistry*; D053719:Tandem Mass Spectrometry; D056811:Unfolded Protein Response / Q000187:drug effects
D000970:Antineoplastic Agents; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D010936:Plant Extracts; D059808:Polyphenols; D020543:Proteome
HT-29 cells; antiproliferative activity; colon cancer; dimethyl labeling; foodomics; mass spectrometry; quantitative proteomics; rosemary extract