Dietary supplementation with the anti-tumour promoter quercetin: its effects on matrix metalloproteinase gene regulation

Dietary modification, especially the consumption of larger amounts of fruit s and vegetables can act to decrease the risk of a variety of human cancers . Quercetin, a bioflavonoid widely distributed in fruits and vegetables has been shown to have a chemoprotective role in cancer, through complex effec ts on signal transduction involved in cell proliferation and angiogenesis. In this study we examined the effects of dietary supplementation of quercet in (30 mg per day) incorporated into a blackcurrant drink. Healthy mate sub jects aged between 33 and 64 years (mean = 47.1 years) received either quer cetin or placebo for 14 days. Blood samples were taken at baseline and upon completion of the study and analysed for full blood count, matrix metallop roteinase-2 (MMP-2), tissue inhibitor of matrix metalloproteinse-1 and -2 ( TIMP-1 and -2) plasma levels using ELISA techniques. RNA was extracted from the peripheral blood lymphocytes and reverse transcriptase-polymerase chai n reaction (RT-PCR) carried out for NIMP-2 and TIMP-1, TIMP-2 gene expressi on determination. Supplementation of the diet with quercetin did not alter the MMP-2 or TIMP-2 gene transcription or plasma protein levels of the heal thy subjects in this study. The TIMP-1 gene transcription and plasma protei n levels (311 +/- 70 ng/ml at baseline to 183 +/- 35 ng/ml post-supplementa tion, P < 0.05) of the subjects in this study were, however, significantly decreased following quercetin supplementation. This is an interesting resul t, as there is some controversy over the functions of TIMP-1 in tumour prog ression. In certain model systems, artificially increased TIMP-1 levels pre vent or decrease tumour growth. However, in other studies high levels of TI MP-1 have been correlated with aggressive disease and poor prognosis in pat ients with certain malignancies. This study has outlined a potential role f or the anti-tumour promoter quercetin as a dietary mediator of the carcinog enic cascade. (C) 2001 Elsevier Science B.V. All rights reserved.