Organ-specific exposure and response to sulforaphane, a key chemopreventive ingredient in broccoli: implications for cancer prevention.
نویسندگان
چکیده
Naturally occurring sulforaphane (SF) has been extensively studied for cancer prevention. However, little is known as to which organs may be most affected by this agent, which impedes its further development. In the present study, SF was administered to rats orally either in a single dose or once daily for 7 d. Tissue distribution of SF was measured by a HPLC-based method. Glutathione S-transferase (GST) and NAD(P)H:quinone oxidoreductase 1 (NQO1), two well-known cytoprotective phase 2 enzymes, were measured using biochemical assays to assess tissue response to SF. SF was delivered to different organs in vastly different concentrations. Tissue uptake of SF was the greatest in the stomach, declining rapidly in the descending gastro-intestinal tract. SF was rapidly eliminated through urinary excretion, and urinary concentrations of SF equivalents were 2-4 orders of magnitude higher than those of plasma. Indeed, tissue uptake level of SF in the bladder was second only to that in the stomach. Tissue levels of SF in the colon, prostate and several other organs were very low, compared to those in the bladder and stomach. Moreover, induction levels of GST and NQO1 varied by 3- to 6-fold among the organs of SF-treated rats, though not strictly correlated with tissue exposure to SF. Thus, there is profound organ specificity in tissue exposure and response to dietary SF, suggesting that the potential chemopreventive benefit of dietary SF may differ significantly among organs. These findings may provide a basis for prioritising organs for further chemopreventive study of SF.
منابع مشابه
Keap1-nrf2 signaling: a target for cancer prevention by sulforaphane.
Sulforaphane is a promising agent under preclinical evaluation in many models of disease prevention. This bioactive phytochemical affects many molecular targets in cellular and animal models; however, amongst the most sensitive is Keap1, a key sensor for the adaptive stress response system regulated through the transcription factor Nrf2. Keap1 is a sulfhydryl-rich protein that represses Nrf2 si...
متن کاملDietary isothiocyanates as confounding factors in the molecular epidemiology of colon cancer.
In this issue, Lin et a!. ( 1) show convincing statistics that subjects exposed to dietary broccoli who have a GSTM 12 null phenotype are less susceptible to colon cancer than those who are GSTMI positive. The expected effect of a GSTM1 null phenotype is greater, not less, susceptibility to cancers due to reduced carcinogen detoxification by GSTM1 (2, 3). Broccoli reverses this outcome for two ...
متن کاملBioassay Methods useful to select the natural product cancer chemopreventive agents
Prevention of malignant disease such as cancer is obviously much more important than therapy, so primary prevention tactics should be invoked with the greatest possible effort. Because delaying a disease such as cancer is somehow equivalent to cure and it is now generally accepted that cancer can be managed through chemopreventive interventions. Since a considerable number of known cancer chemo...
متن کاملEpigenetic impact of dietary isothiocyanates in cancer chemoprevention.
PURPOSE OF REVIEW There is growing evidence that cancer chemopreventive agents including isothiocyanates (ITCs) from cruciferous vegetables target epigenetic mechanisms. The present report will summarize novel findings of ITCs on histone deacetylase activity, DNA methylation, and short noncoding microRNAs, focusing on sulforaphane (SFN) from broccoli and phenethylisothiocyanate from watercress....
متن کاملKinetics of sulforaphane in mice after consumption of sulforaphane-enriched broccoli sprout preparation.
SCOPE Sulforaphane (SF) is a natural isothiocyanate in broccoli sprouts with cancer chemopreventive activity. This study is aimed to use different methods to develop broccoli sprout preparations to compare their ability to deliver SF to the mice and to evaluate the kinetics and biodistribution of SF. METHODS AND RESULTS The SF-enriched sprout preparation generated by two-step procedure (quick...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- The British journal of nutrition
دوره 109 1 شماره
صفحات -
تاریخ انتشار 2013