The cruciferous nitrile crambene has bioactivity similar to sulforaphane when administered to Fischer 344 rats but is far less potent in cell culture.
The anticarcinogenic properties of broccoli are believed to be due to modification of detoxification enzymes by a group of isothiocyanates, hydrolysis products of glucosinolates, particularly sulforaphane. We previously showed that the nitrile crambene (1-cyano-2-hydroxy-3-butene), present in most Brassica vegetables, induces hepatic quinone reductase activity when administered to rats. In this study, we compared the effects of seven daily oral doses of crambene (50 mg/kg rat/day) and sulforaphane (50 mg/kg rat/day) on induction of hepatic quinone reductase activity in Fischer 344 rats. The two treatments produced similar effects, with crambene and sulforaphane producing 1.5- and 1.7-fold induction in hepatic quinone reductase activity, respectively. Additionally, we evaluated the effect of crambene on quinone reductase activity in Hepa 1c1c7 cells, because this system had been shown to possess high sensitivity to sulforaphane and is commonly used for screening anticarcinogenic compounds. Crambene (5 mM) induced quinone reductase activity and caused cell cycle arrest in the G2/M phase in mouse Hepa 1c1c7 cells, rat H4IIEC3 cells, and human Hep G2 cells (> 95% viability). Doses of crambene needed for induction of quinone reductase in cell culture were approximately 100-fold greater than effective doses of sulforaphane. These findings indicate that hepatoma cell lines may not accurately reflect relative potency of anticarcinogens in Fischer 344 rats.
Keck
Anna-Sigrid
AS
Division of Nutritional Sciences, University of Illinois, Urbana, IL 61801, USA.
Staack
Richard
R
Jeffery
Elizabeth H
EH
D000475:Alkenes / Q000494:pharmacology*; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects; D017879:Isothiocyanates; D008297:Male; D051379:Mice; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000096:biosynthesis; D009570:Nitriles / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D013454:Sulfoxides; D013861:Thiocyanates / Q000494:pharmacology*
D000475:Alkenes; D016588:Anticarcinogenic Agents; D017879:Isothiocyanates; D009570:Nitriles; D013454:Sulfoxides; D013861:Thiocyanates; C055903:1-cyano-2-hydroxy-3-butene; D016660:NAD(P)H Dehydrogenase (Quinone); C016766:sulforaphane