Carcinogenesis, Vol. 21, No. 6, 1183-1189,
June 2000
© 2000 Oxford University Press
Molecular Epidemiology and Cancer Prevention |
Prevention of colonic aberrant crypt foci by dietary feeding of garcinol in male F344 rats
Department of Pathology and
1 Department of Serology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa 920-0293,
2 Research and Development Division, Kikkoman Corporation, 399 Noda, Noda City, Chiba 278-0037,
3 Department of Biotechnological Science, Faculty of Biology-Oriented Science and Technology, Kinki University, Iwade-Utita, Wakayama 649-6493 and
4 Division of Applied Life Science, Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan
The modifying effects of dietary feeding of a polyisoprenylated benzophenone, garcinol, isolated from Garcinia indica fruit rind on the development of azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) were investigated in male F344 rats. We also assessed the effects of garcinol on proliferating cell nuclear antigen (PCNA) index in ACF and activities of detoxifying enzymes of glutathione S-transferase (GST) and quinone reductase (QR) in liver. In addition, we examined the effects of garcinol on 12-O-tetradecanoylphorbol-13-acetate-induced O2– generation in differentiated human promyelocytic HL-60 cells and lipopolysaccharide (LPS)- and interferon (IFN)-
-induced nitric oxide (NO) generation in mouse macrophage RAW 264.7 cells. Western blotting analysis of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression was done in LPS- and IFN--treated mouse macrophage RAW 264.7 cells. Rats were given subcutaneous injections of AOM (15 mg/kg body wt) once a week for 3 weeks to induce ACF. They also received the experimental diet containing 0.01 or 0.05% garcinol for 5 weeks, starting 1 week before the first dosing of AOM. AOM exposure produced 97 ± 15 ACF/rat at the end of the study (week 5). Dietary administration of garcinol caused significant reduction in the frequency of ACF: 72 ± 15 (26% reduction, P < 0.01) at a dose of 0.01% and 58 ± 8 (40% reduction, P < 0.001) at a dose of 0.05%. Garcinol administration significantly lowered PCNA index in ACF. Feeding of garcinol significantly elevated liver GST and QR activities. In addition, garcinol could suppress O2– and NO generation and expression of iNOS and COX-2 proteins. These findings might suggest possible chemopreventive ability of garcinol, through induction of liver GST and QR, inhibition of O2– and NO generation and/or suppression of iNOS and COX-2 expression, on colon tumorigenesis.
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