Objective: To study the Inhibition of proteasome activity by the dietary flavonoid Quercetin associated with growth inhibition in cultured breast cancer cells and xenografts. Methods: MCF-7 breast cancer cell cultures and xenografts were treated with quercetin, carried out by following measurement of reduced cellular viability/proliferation, proteasome inhibition, and apoptosis induction. Inhibition of the proteasome was decided by levels of the proteasomal chymotrypsin-like activity, by target proteins, and by accumulation of proteasome target proteins in extracts of the treated cells or tumours. Apoptotic cell inhibition was measured by capase-3/caspase-7 activation, poly (ADP-ribose) polymerase cleavage, and immunohistochemistry for terminal nucleotidyl transferase. Results: This result is carried out for the first time by us that quercetin inhibits the proteasomal chymotrypsin-like activity and induces apoptosis not only in cultured MCF-7 cell lines but also in MCF-7 xenografts moreover, while quercetin has antibreast tumour activity and no toxicity was observed to the tested animals. Conclusion: We have shown that quercetin is an effective proteasome inhibitor in cultured breast cancer cells and in breast cancer xenografts. Furthermore, quercetin induces apoptotic cell death in human breast cancer cells and exhibits anticancer activities in tumours. The results suggest its potential benefits in breast cancer prevention and treatment.
Key words: Breast cancer, MCF-7, Proteasome activity, Quercetin, Xenografts.