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Impaired Expression and Function of Signaling Pathway Enzymes by Anthocyanins: Role on Cancer Prevention and Progression

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Abstract:

Anthocyanins (Greek antos, flower and kyanos, blue) are part of a widespread group of plant constituents, collectively known as flavonoids, which occur in the western diet at relatively high concentrations and own a variety of pharmacological properties which make them potential anti-inflammatory and cancer agents. Besides their ability to scavenge reactive oxygen species, anthocyanins exhibit anticancer effects through impaired expression and function of enzymes, most of which are involved in abnormal activation of signaling pathways leading to cancer cell growth and progression. Antiproliferative and antiangiogenetic properties of anthocyanins encompass inhibition of phosphorylation of receptor tyrosine kinases (EGFR, VEGFR, Met receptor, PDGFR) and down-regulation of downstream signaling cascades, impaired activity of cAMP-specific phosphodiesterases, chymotrypsin-like proteasome activity, ornithine decarboxylase and cyclin-dependent kinases/cyclin complex. Transcription activity of NF-κB, involved in the carcinogenesis process, is affected by anthocyanins through inhibition of the IκB kinase complex phosphorylation. The antiproliferative activity is dependent on the presence of hydroxyl groups on ring B of the anthocyanin molecule. Anthocyanins influence cancer cell invasion as well, through the decrease of metalloproteinases and plasmin activity. Finally, inhibition of cyclooxygenase activity may counteract a number of characteristics of tumor progression and metastasis. Conversely, one potential drawback of the anthocyanin's effect is their inhibitory activity on topoisomerases I and II. This review will deal with the current knowledge on the anthocyanins ability to hamper the expression and function of signaling pathway enzymes involved in cancer development and discuss anthocyanins preventive/therapeutic potential against human cancers.





Document Type: Research Article

Publication date: December 1, 2009

More about this publication?
  • Current Enzyme Inhibition aims to publish all the latest and outstanding developments in enzyme inhibition studies with regards to the mechanisms of inhibitory processes of enzymes, recognition of active sites, and the discovery of agonists and antagonists, leading to the design and development of new drugs of significant therapeutic value. Each issue contains a series of timely, in-depth reviews written by leaders in the field, covering a range of enzymes that can be exploited for drug development. Current Enzyme Inhibition is an essential journal for every pharmaceutical and medicinal chemist who wishes to have up-to-date knowledge about each and every development in the study of enzyme inhibition.
ben/cei/2009/00000005/00000004/art00002
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