Citrus bioactive compounds influencing phase II detoxifying enzymes: potential for cancer chemoprevention

Abstract

Several cell culture and animal studies demonstrated that citrus limonoids have protective effects against certain types of cancer. These chemopreventive properties of citrus limonoids are attributed to the induction of phase II enzyme, glutathione Stransferase (GST). In the current study, six citrus limonoids and two modified limonoids were utilized for the evaluation of NAD(P)H: quinone reductase (QR) activity and glutathione S-tranferase (GST) activity against 1-chloro-2,4-dinitrobenzene (CDNB) and 4-nitroquinoline 1-oxide (4NQO) in A/J female mice. In liver, limonoids that induced phase II enzyme activity were limonin-7- methoxime (32% CBNB), (270% 4NQO), (65% QR); and deacetylnomilin (180% QR). In stomach, limonin-7-methoxime (51% 4NQO); deacetyl nomilinic acid glucoside (55% 4NQO), nomilin (58% CDNB), (75% 4NQO); isoobacunoic acid (25% CDNB); deacetylnomilin (19% CDNB); limonoid mixture (45% 4NQO), (200% QR). Furthermore, in intestine, nomilin (280% 4NQO); deacetylnomilin (73% 4NQO), (22% QR); and the limonoid mixture (93% 4NQO) increase enzymatic activity. Finally in lung, deacetyl nomilinic acid glucoside (67% CDNB); limonin-7-methoxime (32% QR); and defuran limonin (45% QR) diplayed induction properties. Furthermore, D-glucaric acid (GA), a chemoprotective compound found in fruits and vegetables, was quantified using High Performance Liquid Chromatography (HPLC) grapefruit. Nine widely used grapefruit varieties were analyzed for the levels of D-glucaric acid. Seasonal levels of GA in each of the grapefruit varieties tested were found to be Thompson (58.36-126.8 mg/100ml), Henderson (29.6-49.7 mg/100ml), Rio Red (40.0-58.8mg/100ml), Star Ruby (25.5-46.7 mg/100ml), I-48 (26.6-58.3 mg/100ml), Ruby Red (49.3-63.0 mg/100ml), Ray’s Ruby (58.2-72.1 mg/100ml), Marsh (53.7-65.8 mg/100ml) and Duncan (50.17 mg/100ml). The HPLC method developed for the quantification of D-glucaric acid was found to be simple, fast, and reproducible. Additionally, the labor intensity and cost of sample preparation were greatly reduced.