Inhibition of pancreatic cancer cell migration by plasma anthocyanins isolated from healthy volunteers receiving an anthocyanin-rich berry juice
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Pancreatic cancer is an aggressive cancer type, of which the most important characteristics are migration and metastasis. Anthocyanins (ACN) are discussed to be protective phytochemicals; however, up to now only scarce data are available regarding their effects on cancer prevention. In this study, we aimed to determine whether ACN and their metabolites from plasma (PAM), isolated from blood of healthy volunteers after ingestion of an ACN-rich juice, are effective in modulating cancer cell migration in vitro.
PAM were isolated from blood of healthy volunteers (n = 10) after consumption of an ACN-rich berry juice. Before ingestion (PAM0min) and after 60 min (PAM60min), blood was taken and PAM were isolated from plasma by solid-phase extraction. Migration of pancreatic cancer cells PANC-1 and AsPC-1 was assayed in a Boyden chamber. The influence of PAM on cellular reactive oxygen species (ROS) or mitochondria-specific ROS was measured fluorimetrically. mRNA expression levels of matrix metalloproteinases (MMP-2 and MMP-9) and NF-κB mRNA were determined by real-time PCR.
After application of PAM60min to PANC-1, we observed a reduced cell migration, which was associated with reduced levels of endogenously generated ROS concomitant with reduced NF-κB as well as MMP-2 and MMP-9 mRNA expression levels. In AsPC-1 cells, however, migration was not affected by PAM60min.
It can be assumed that physiologically relevant ACN and their metabolites were able to inhibit pancreatic cancer cell migration in dependency of the phenotype of cells and may thus deserve further attention as potential bioactive phytochemicals in cancer prevention.
KeywordsGrapes and bilberries Anthocyanins Pancreatic cancer cells Metalloproteinases Migration
This research was funded by the German Ministry of Education and Research (BMBF) as part of the research consortium ANTHONIA (Grant Number 0315379A). The authors would like to thank the Barbara and Reinhard Bretzel Foundation for awarding the subproject on pancreatic cancer cells. S. R. and C. K. were the overall principal investigator of the study responsible for the overall outline of the project and the study design. S. K performed the assays for ROS detection and FACS analyses and wrote the first draft of the manuscript. All authors approved its final version before submission and have no conflicts of interest. Cordula Becker assisted the SPE separation of the ACN from plasma, and Nadine Metz and Nicole Tscherney were responsible for analysis the migration and RNA extraction. Marcel Zoremba has done the real-time PCR.
Compliance with ethical standards
The study protocol was approved by the Institutional Ethics Committee (registration number 13/10), and all participants provided written informed consent. We are deeply grateful to all volunteers who participated in the study.
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