Dietary induction of NQO1 increases the antitumour activity of mitomycin C in human colon tumours in vivo. Begleiter A, Leith MK, Thliveris JA, Digby T. [1] 1Department of Internal Medicine, Manitoba Institute of Cell Biology, CancerCare Manitoba, University of Manitoba, 675 McDermot Avenue, Winnipeg, Manitoba, Canada R3E 0V9 [2] 2Department of Pharmacology and Therapeutics, Manitoba Institute of Cell Biology, CancerCare Manitoba, University of Manitoba, 675 McDermot Avenue, Winnipeg, Manitoba, Canada R3E 0V9. The bioreductive antitumour agent, mitomycin C (MMC), requires activation by reductive enzymes like NAD(P)H:quinone oxidoreductase 1 (NQO1). We used a novel approach to increase MMC efficacy by selectively inducing NQO1 in tumour cells in vivo. CD-1 nude mice were implanted with HCT116 cells, and fed control diet or diet containing 0.3% of the NQO1 inducer, dimethyl fumarate (DMF). The mice were then treated with saline, 2.0, 3.5 or 2.0 mg kg(-1) MMC and dicoumarol, an NQO1 inhibitor. The DMF diet increased NQO1 activity by 2.5-fold in the tumours, but had no effect in marrow cells. Mice given control diet/2.0 mg kg(-1) MMC had tumours with the same volume as control mice; however, mice given DMF diet/2.0 mg kg(-1) MMC had significantly smaller tumours. Tumour volumes in mice given DMF/2.0 mg kg(-1) MMC were similar to those in mice given control diet/3.5 mg kg(-1) MMC. Tumour inhibition was partially reversed in mice given DMF/2.0 mg kg(-1) MMC and dicoumarol. DMF diet/2.0 mg kg(-1) MMC treatment did not increase myelosuppression and did not produce any organ toxicity. These results provide strong evidence that dietary inducers of NQO1 can increase the antitumour activity of bioreductive agents like MMC without increasing toxicity. British Journal of Cancer advance online publication, 5 October 2004; doi:10.1038/sj.bjc.6602171 www.bjcancer.com. PMID: 15467770 [PubMed - as supplied by publisher] "Dimethylfumarate, a compound derived from fruits and vegetables, could be used to enhance the effects of mitomycin C in bladder and colon cancer, Canadian researchers reported". (REUTERS) Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. You can help raise awareness of CAM.