Quercetin glucuronides inhibited 2-aminofluorene acetylation in human acute myeloid HL-60 leukemia cells

Department of Parasitology, China Medical College, Taichung, Taiwan, Republic of China.
Phytomedicine (Impact Factor: 3.13). 11/2002; 9(7):625-31. DOI: 10.1078/094471102321616436
Source: PubMed


Our earlier study has demonstrated that following the exposure of rat to the arylamine carcinogen 2-aminofluorene, DNA-2-aminofluorene adducts were found in the target tissues liver, bladder, colon, lung and also in circulating leukocytes (lymphocytes and monocytes). The result also demonstrated that orally treated antioxidants decreased N-acetylation of 2-aminofluorene in target tissues and leukocytes. Therefore, this study investigated whether quercetin glucuronides could affect N-acetylation of 2-aminofluorene in human acute myeloid leukemia HL-60 cells. Evidence is presented here that human leukemia cells are capable of acetylating 2-aminofluorene. Quercetin glucuronides did inhibit 2-aminofluorene acetylation in intact cells. The results also indicated that quercetin glucuronides induced cytotoxicity in dose-dependent manner in the examined human acute myeloid leukemia HL-60 cells.

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    • "For example, conjugation has been shown to detrimentally affect the ability of quercetin to inhibit xanthine oxidase and lipoxygenase enzyme activities in vitro, although the loss of potency was heavily dependent on the position of conjugation; the 3'-and 4'- glucuronides were only slightly less effective inhibitors of xanthine oxidase (Day et al., 2000). Quercetin glucuronides have also been shown to inhibit the N-acetylation of the arylamine carcinogen 2-aminofluorene by human acute myeloid leukaemia (HL-60) cells (Kuo et al., 2002), inhibit lung cancer cell growth via cell cycle arrest and induction of apoptosis (Yang et al., 2006), prevent angiotensin-II-induced vascular cell hypertrophy in cultured rat aortic smooth muscle cells via inhibition of JNK and AP-1 signalling pathways (Yoshizumi et al., 2002) and down-regulate transcription of human cyclooxygenase-2 (COX-2) (O'Leary et al., 2004; de Pascual-Teresa et al., 2004). In contrast, Donnini et al. (2006) provide evidence that whereas quercetin and quercetin-3-glucuronide inhibited vascular endothelial growth factor (VEGF)-induced changes in cell functions and angiogenesis, quercetin-3'-sulfate promoted cell proliferation and angiogenesis. "
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    • "Flavonoid glucuronides are substrates for recombinant human β-glucuronidase; similarly, it has been shown that quercetin glucuronides can be deconjugatad by cell-free extracts of human liver, small intestine and blood neutrophils (O'Leary et al., 2001, 2003). It has been shown that quercetin glucuronides prepared from the serum of rabbit induce cytotoxicity in dose-dependent manner in human myeloid leukaemia HL-60 cells (Kuo et al., 2002). "
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    • "Quercetin (3,3 0 ,4 0 ,5,7-pentahydroxyflavone, QU) is one of the major dietary flavonoids, found in a broad range of fruits, vegetables and beverages such as tea and wine, with a daily intake in Western countries of 25–30 mg (Hollman et al. 1997; Morand et al. 1998), and has been found to show anticancer activity in different cancer cells and in animals (Chen et al. 2004a, b; Cipak et al. 2003; Kaneuchi et al. 2003; Liesveld et al. 2003; Chan et al. 2003; Lee et al. 2002; Mouria et al. 2002; Kuo et al. 2002; Feng et al. 2001; Kim et al. 2000; Kawaii et al. 1999; Kang et al. 1997; Uddin et al. 1995). Among the polyphenols, QU is one of the most potent antioxidants, as demonstrated in different in vitro and in vivo studies (Prior 2003; Duthie et al. 2000; Russo et al. 1999; Bors et al. 1990; Morand et al. 1998; Hollman et al. 1997), and this antioxidant activity is critically involved in its anticancer activity (Chen et al. 2004a, b; Duthie et al. 2000; Feng et al. 2001). "
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