Abstract
In this study, the effects of bioactive compounds derived from vegetables of the Brassica genus (Brassicaceae) including 2-phenylethyl isothiocyanate (PEITC), indole-3-carbinol
(I3C), and indolo[3,2-b]carbazole (ICZ), on the inhibition of NO production in RAW 264.7 cells were explored.
The results indicated that PEITC and I3C inhibited lipopolysaccharide (LPS)- and interferon-γ
(IFN-γ)-induced NO production in RAW 264.7 cells, and this inhibition was in accordance
with lowering the expression of iNOS protein and mRNA. On the contrary, ICZ, a derivative
of I3C, had no significant effect on the stimulated NO production. In conclusion,
the Brassica plants derivatives, PEITC and, to a lesser extent, I3C inhibit the LPS/IFN-γ-induced
NO production by lowering iNOS protein and mRNA expression in RAW 264.7 cells, in
which the PEITC had a more potent inhibitory effect. Nevertheless, ICZ exhibits no
inhibitory effect on the activated NO production (Indole-3-carbinol = indole-3-methanol).
Key words
Brassicaceae
- indole - isothiocyanate - nitric oxide - inducible nitric oxide synthase - RAW 264.7
macrophages
References
- 1
Davis K L, Martin E, Turko I V, Murad F.
Novel effects of nitric oxide.
Annu Rev Pharmacol Toxicol.
2001;
41
203-36
- 2
Kroncke K D, Fehsel K, Kolb-Bachofen V.
Inducible nitric oxide synthase in human diseases.
Clin Exp Immunol.
1998;
113
147-56
- 3
Tamir S, Tannenbaum S R.
The role of nitric oxide (NO) in the carcinogenic process.
Biochim Biophys Acta.
1996;
1288
F31-6
- 4
Graham S, Mettlin C.
Diet and colon cancer.
Am J Epidemiol.
1979;
109
1-20
- 5
Stoewsand G S.
Bioactive organosulfur phytochemicals in Brassica oleracea vegetables - a review.
Food Chem Toxicol.
1995;
33
537-43
- 6
McDanell R, McLean A EM, Hanley A B, Heaney R K, Fenwick G R.
Chemical and biological properties of indole glucosinolates (glucobrassicins): a review.
Food Chem Toxicol.
1988;
26
59-70
- 7
Kwon C -S, Grose K R, Riby J, Chen Y -H, Bjeldanes L F.
In vivo production and enzyme-inducing activity of indolo[3,2-b]carbazole.
J Agric Food Chem.
1994;
42
2536-40
- 8
Zhang Y, Talalay P.
Anticarcinogenic activities of organic isothiocyanates: chemistry and mechanisms.
Cancer Res.
1994;
54(suppl)
1976S-81S
- 9 Robinson B. The Fischer indolisation of cyclohexane-1,4-dione bisphenylhydrazone. J
Chem Soc 1963: 3097-9
- 10
Privat C, Lantoine F, Bdeioui F, van Brussel E M, Devynck J, Devynck M A.
Nitric oxide production by endothelial cells: comparison of three methods of quantification.
Life Sci.
1997;
61
1193-202
- 11
Noda T, Amano F.
Differences in nitric oxide synthase activity in a macrophage-like cell line, RAW
264.7 cells, treated with lipopolysaccharide (LPS) in the presence or absence of interferon-γ
(IFN-γ): possible heterogeneity of iNOS activity.
J Biochem.
1997;
121
38-46
- 12
Tsai S H, Lin-Shiau S Y, Lin J K.
Suppression of nitric oxide synthase and the down-regulation of the activation of
NFκB in macrophages by resveratrol.
Brit J Pharmacol.
1999;
126
673-80
- 13
Bradfield C A, Bjeldanes L F.
Effect of dietary indole-3-carbinol on intestinal and hepatic monooxygenase, glutathione
S-transferase and epoxide hydrolase activities in the rat.
Food Chem Toxicol.
1984;
22
977-82
- 14
Guo Z, Smith T J, Wang E, Sadrieh N, Ma Q, Thomas P E. et al .
Effects of phenethyl isothiocyanate, a carcinogenesis inhibitor, on xenobiotic-metabolizing
enzymes and nitrosamine metabolism in rats.
Carcinogenesis.
1992;
13
2205-10
- 15
Bonnesen C, Eggleston I M, Hayes J D.
Dietary indoles and isothiocyanates that are generated from cruciferous vegetables
can both stimulate apoptosis and confer protection against DNA damage in human colon
cell lines.
Cancer Res.
2001;
61
6120-30
- 16
Ge X, Fares F A, Yannai S.
Induction of apoptosis in MCF-7 cells by indole-3-carbinol is independent of p53 and
Bax.
Anticancer Res.
1999;
19
3199-204
- 17
Ohshima H, Bartsch H.
Chronic infections and inflammatory processes as cancer risk factors: possible role
of nitric oxide in carcinogenesis.
Mutation Res.
1994;
305
253-64
- 18
Grose K R, Bjeldanes L F.
Oligomerization of indole-3-carbinol in aqueous acid.
Chem Res Toxicol.
1992;
5
188-93
- 19
Bjeldanes L F, Kim J -Y, Grose K R, Bartholomew J C, Bradfield C A.
Aromatic hydrocarbon responsiveness-receptor agonists generated from indole-3-carbinol
in vitro and in vivo: comparisons with 2,3,7,8-tetrachlorodibenzo-p-dioxin.
Proc Natl Acad Sci USA.
1991;
88
9543-7
- 20
Liu H, Wormke M, Safe S H, Bjeldanes L F.
Indolo[3,2-b]carbazole: a dietary-derived factor that exhibits both antiestrogenic and estrogenic
activity.
J Natl Cancer Inst.
1994;
86
1758-65
Dr. Yue-Hwa Chen
Taipei Medical University
Graduate Institute of Nutrition and Health Sciences
250 Wu-Hsing Street
Taipei 110
Taiwan
Republic of China
Telefon: +886-2-27361661 ext. 6555 ext. 118
Fax: +886-2-27373112
eMail: yuehwa@tmu.edu.tw