Table 1.
Chemopreventive Activity of sulforaphane in mice: Modulation by Nrf2.
| Organ site | Species strain | Carcinogen/mutation | SFN Formulation or dose | Endpoints measured | Reference |
|---|---|---|---|---|---|
| Wild-type vs. NRF2-knockout mice | |||||
| Skin | Mouse ♀ C57Bl6 | DMBA | 100 nmol SFN, topical, q.d. X 14 before DMBA | Reduced tumor incidence in WT with SFN, but not NRF2 KO mice | Xu et al., 2006 |
| Stomach | Mouse ♀ C57Bl/6 | 4NQO | 7.5 μmol SFN q.d. X 9 before/after B[a]P | Reduced tumor incidence in WT with SFN, but not NRF2 KO mice | Fahey et al., 2002 |
| Colon | Mouse ♀ C57Bl/6J | 4NQO | 400 ppm SFN in the diet | Reduced tumor multiplicity and burden in WT mice with SFN; NRF2+/- mice less sensitive than WT mice & no protection by SFN | Rajendran et al., 2015 |
| Oral | Mouse ♀ C57Bl/6 | 4NQO | 6 μmol SFN/mouse; 3X wk, p.o. for 16 wk | SFN protects WT at 24 wks | Bauman et al., 2016 |
| Mouse ♀ C57Bl/6J | 4NQO | No treatment | NRF2 KO more sensitive: KEAP1-KD more resistant than WT at 24 wks | Ohkoshi et al., 2013 | |
| Skin | Mouse ♀ SKH-1 | UV | 100 μL broccoli sprout extract containing 1 μmol SFN topical | Reduced tumor incidence, multiplicity & burden | Dinkova-Kostova et al., 2006 |
| Mouse ♀ SKH-1 | UV | broccoli sprout extract providing 10 μmol glucoraphanin daily in the diet | Reduced tumor incidence, multiplicity & burden | Dinkova-Kostova et al., 2010 | |
| Mouse ♀ SKH-1 | UV | No treatment | NRF2 KO much more sensitive than KEAP1-KD | Knatko et al., 2016 | |
| Wild-type rodents only | |||||
| Skin | Mouse ♀ CD-1 | DMBA→ TPA | 1, 5 or 10 μmol SFN topical before TPA | Reduced tumor incidence & multiplicity | Gills et al., 2006 |
| Skin | Mouse ♀ SKH-1 | UV | 2.5 μmol SFN topical | Reduced tumor incidence & multiplicity | Dickinson et al., 2009 |
| Colon | Mouse ♂ C57Bl/6J+/min | Apcmin | ∼6 μmol SFN/d (443 ppm) in diet for wks 6–16 | Reduced tumor multiplicity | Myzak et al., 2006 |
| Colon | Mouse | Apcmin | 300 or 600 ppm SFN in diet for wks 8–11 | Dose-dependent reduction in tumor multiplicity | Hu et al., 2006 |
| Colon | Mouse ♂ | Apcmin | 600 ppm SFN in diet for wks 5–15 | Reduced tumor multiplicity | Shen et al., 2007 |
| Lung | Mouse ♀ A/J | B[a]P + NNK | 3 mmol/kg; 20 wks after carcinogen administration, fed diet containing SFN wks 21–42. | Reduced tumor incidence | Conaway et al., 2005 |
| Prostate | Mouse ♂ | TRAMP | 6 μmol SFN/mouse; 3X wk, p.o. for 17–19 wk | Reduced tumor incidence | Singh et al., 2009 |
| Prostate | Rat ♂ | TRAMP | 60 and 240 mg broccoli sprouts/mouse/day, p.o., for 16 wk | Reduced tumor incidence | Keum et al., 2009 |
| Bladder | Rat ♀ | BBN | lyophilized broccoli sprout extract in diet to provide isothiocyanate doses of 40 and 160 μmol/kg body weight/d | Reduced tumor incidence, multiplicity and size | Munday et al., 2008 |
Abbreviations: KO, knockout, KD, knockdown; WT, wild-type; SFN, sulforaphane; DMBA, dimthylbenz[a]anthracene; TPA, 12-O-tetradecanoylphorble ester; 4NQO, 4-nitroqquinoline-1-oxide); UV, ultraviolet light; B[a]P, benzo[a]pyrene; AOM, azoxymethane; DMH, dimethylhydrazine; N-OH-BBN, N-butyl-N-(4-hydroxybutyl) nitrosamine; TRAMP, transgenic adenocarcinoma of mouse prostate; NNK: 4-(methylnitrosamino)-1-(3-pyridyl)–1-butanone.