Impaired expression and function of signaling pathway enzymes by anthocyanins: Role on cancer prevention and progression

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.