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.
"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. "
[Show abstract][Hide abstract] ABSTRACT: Although excessive consumption of ethanol in alcoholic beverages causes multi-organ damage, moderate consumption, particularly of red wine, is protective against all-cause mortality. These protective effects could be due to one or many components of the complex mixture of bioactive compounds present in red wine including flavonols, monomeric and polymeric flavan-3-ols, highly colored anthocyanins as well as phenolic acids and the stilbene polyphenol, resveratrol. The therapeutic potential of resveratrol, firstly in cancer chemoprevention and then later for cardioprotection, has stimulated many studies on the possible mechanisms of action. Further indications for resveratrol have been developed, including the prevention of age-related disorders such as neurodegenerative diseases, inflammation, diabetes, and cardiovascular disease. These improvements are remarkably similar yet there is an important dichotomy: low doses improve cell survival as in cardio- and neuro-protection yet high doses increase cell death as in cancer treatment. Fewer studies have examined the responses to other components of red wine, but the results have, in general, been similar to resveratrol. If the nonalcoholic constitutents of red wine are to become therapeutic agents, their ability to get to the sites of action needs to be understood. This mini-review summarizes recent studies on the possible mechanisms of action, potential therapeutic uses, and bioavailability of the nonalcoholic constituents of alcoholic beverages, in particular resveratrol and other polyphenols.
Alcoholism Clinical and Experimental Research 07/2009; 33(9):1513-23. DOI:10.1111/j.1530-0277.2009.00989.x · 3.21 Impact Factor
"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). "
[Show abstract][Hide abstract] ABSTRACT: The chemical and pharmaceutical studies carried out on species from Polygonum L. genus showed biological activity both of the extracts and the components isolated from them. These results were the impulse to examine Polygonum amphibium L.
The aim of this study was the isolation of active components from methanol extract and the determination of their cytotoxic effect on human leukaemic cell lines.
Three flavonoid components from butanol soluble fractions of methanol extract by CC and PC preparative chromatography were isolated. Their structures were established on the basis of 1H, 13C and correlation (DEPT, H-H, COSY, HMQC, HMBC) NMR, UV and FAB-MS spectroscopic techniques. The evaluation of the anti-leukaemic activities of 1 and 2 against Jurkat and HL60 cell lines was carried out in vitro using annexin V fluorescence assay.
Two new flavonoid glucuronides, quercetin-3-O-beta-glucuronide (1) and quercetin-3-O-alpha-rhamnosyl-(1 --> 2)-beta-glucuronide (2), and kaempferol-3-O-alpha-rhamnosyl-(1 --> 2)-beta-glucuronide (3), were isolated from Polygonum amphibium L. It was demonstrated that the glucuronides of quercetin are able to induce apoptosis in the tested human leukaemic cells. These compounds penetrate through cytoplasm to the cellular nucleus of the cultured cells, and give intensive apoptotic responses in the stimulated leukaemic cells. The number of apoptotic cells increased with the concentration (1 nm to 10 microm) of 1 or 2 and periods of exposure (1-3 days).
Compounds 1 and 2 may be considered good candidates for leukaemia chemotherapeutic agents.
"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). "
[Show abstract][Hide abstract] ABSTRACT: Quercetin (QU) is recognized as a promising anticancer drug, but its mechanism remains elusive. Here we found that QU induced human leukemia cell death in a dose-dependent manner. However, it did not show a dose-dependent inhibition on ROS generation (indicated by the level of malondialdehyde, MDA) in the same cells. QU showed similar antioxidant activity at concentrations of 50, 75 and 100 microM. Consistent with that, the antioxidant, N-acetyl-cysteine (NAC) could only further decrease the ROS generation and enhance the cell death triggered by QU at the concentrations less than 50 microM. These results indicate that an additional mechanism is involved in the anticancer activity of high concentrations of QU. When the effect of QU on histone acetylation was studied, QU induced significant histone hyperacetylation at 75 and 100 microM, indicating the possible involvement of histone hyperacetylation in the anticancer activity of high concentrations of QU. This conclusion was supported by the findings that when histone acetylation in the cells treated by QU was increased by different concentrations of TSA, the cell death was significantly enhanced. Our results thus provide the first evidence that QU can induce histone hyperacetylation and this induction of histone hyperacetylation may represent an unrevealed mechanism in its anticancer activity.
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