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Biomedical subjects

Yong Liu

Publications and source records attributed to Yong Liu.

At least 37 records · Page 2Linked to original sources
PubMed2006

Inhibitory effects of antisense phosphorothioate oligodeoxynucleotides on pancreatic cancer cell Bxpc-3 telomerase activity and cell growth in vitro.

AIM: To investigate the effect of telomerase hTERT gene antisense oligonucleotide (hTERT-ASO) on proliferation and telomerase activity of pancreatic cancer cell line Bxpc-3. METHODS: MTT assay was used to detect the effect of different doses of hTERT-ASO on proliferation of Bxpc-3 cell for different times. To study the anti-tumor activity, the cells were divided into three groups: Control group (pancreatic cancer cell Bxpc-3); antisense oligonucleotide (hTERT-ASO) group; and nosense oligonucleotide group decorated with phosphorothioate. Telomerase activity was detected using TRAP-PCR-ELISA. Cell DNA distribution was examined using flow cytometry assay. Cell apoptosis was observed by transmission electron microscope in each group. RESULTS: After treatment with 6 mmol/L hTERT-ASO, cell proliferation was inhibited in dose- and time-dependent manner. The telomerase activity decreased after treatment with hTERT-ASO for 72 h. Flow cytometry showed the cell number of G0/G1 phase increased from 2.7% to 14.7%, the cell number of S phase decreased from 72.7% to 51.0%, and a sub-G1 stage cell apoptosis peak appeared in front of G1 stage. CONCLUSION: Telomerase antisense oligodeoxy-nucleotide can inhibit the proliferation of pancreatic cancer cell line Bxpc-3 and decrease the telomerase activity and increase cell apoptosis rate in vitro.

Apoptosis↗
PubMed2006

To patterned binary polymer brushes via capillary force lithography and surface-initiated polymerization.

An effective approach is described for the synthesis of binary patterned polymer brushes using a combination of capillary force lithography and surface-initiated polymerization. First, the approach calls for an ultrathin polystyrene (PS) mask to be deposited, in a pattern, over a surface to which a layer of polymerization initiator has already been anchored. Next, surface-initiated atom transfer radical polymerization (ATRP) is performed. This can graft the initial polymer brush onto those areas of the surface unprotected by the PS mask. After grafting is complete, the PS mask is removed and a second brush is synthesized on the newly exposed areas.

Acrylamides↗
PubMed2006

[Expression of transforming growth factor-beta1 and basic fibroblast growth factor in articular process cartilages of adolescent idiopathic scoliosis].

OBJECTIVE: To investigate the characteristics of the expression of transforming growth factor-beta(1) (TGF-beta(1)) and basic fibroblast growth factor (bFGF) in the apical articular process cartilages of adolescent idiopathic scoliosis (AIS) patients. METHODS: The specimens of articular processes of 22 AIS patients and 18 congenital scoliosis (CS) patients were collected during operation. The pathology of the processes was observed with H.E staining. Immunohistochemistry and in situ hybridization were adopted to detect the expression of TGF-beta(1) and bFGF. The differences in the pathological changes, and expression of TGF-beta(1) and bFGF between the apical processes and the end processes, the convex processes and the concave processes, and the AIS processes and CS processes. The images of immunohistochemistry and in situ hybridization were input into the image analysis system and were analyzed semi-quantitatively. The SAS (8.01) software was adopted and (128.1 +/- 50.6 vs 165.4 +/- 59.2, 126.5 +/- 47.0 vs 168.3 +/- 46.8; 76.6 +/- 29.9 vs 96.4 +/- 28.4, 73.7 +/- 31.6 vs 101.8 +/- 39.4; 77.1 +/- 52.2 vs 114.4 +/- 59.4, and 69.5 +/- 40.1 vs 109.8 +/- 51.0 (P < 0.05) was defined as the significant levels. RESULTS: The expression of TGF-beta(1) and the expression of bFGF were not significantly different between the AIS patients and the CS patients. The TGF-beta(1) expression in the concave side of the apical vertebrae of the AIS group was 165.4 +/- 59.2, significantly higher than that in the convex sides (128.1 +/- 50.6, P = 0.03), and the TGF-beta(1) expression in the concave side of the apical vertebrae of the CS group was 168.3 +/- 46.8, significantly higher than that of the convex side (126.5 +/- 47.0, P = 0.02). However, there was no statistically significant differences in the TGF-beta(1) expression between the concave and convex sides of the upper and lower end vertebrae and between the upper and lower end vertebrae. The bFGF expression in the concave side of the apical vertebrae of the AIS group, and the bFGF expression in the concave side of the apical vertebrae of the CS group was 101.8 +/- 39.4, significantly higher than that of the convex side (73.7 +/- 31, P = 0.02). However, there were no statistically significant differences in the bFGF expression between the concave and convex sides of the upper and lower end vertebrae and between the upper and lower end vertebrae. CONCLUSION: The cartilages of the apical processes show some signs of regression and hypoplasia in AIS patients, especially at the concave side in comparison with the convex side. Increase of TGF-beta(1) and bFGF in the concave sides of apical processes in AIS may be the results of reconstruction of extracellular matrix and the compensation reactions which are caused by abnormal biomechanical forces, especially compressive stresses.

Adolescent↗
PubMed2006

Inhibitory effect of medroxyprogesterone acetate on human liver cytochrome P450 enzymes.

OBJECTIVE: Medroxyprogesterone acetate (MPA), frequently used in contraception and chemotherapy, was involved in a report of drug-drug interaction (DDI) when co-administrated with phenytoin, doxifluridine and cyclophosphamide. In order to clarify the mechanism of such interaction, an in vitro study was undertaken to evaluate MPA's potential to inhibit cytochrome P450 (CYP) enzymes. METHODS: Inhibitory effects of MPA on seven CYPs, including CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2D6, CYP2E1 and CYP3A4, were conducted in human liver microsomes. Time- and NADPH-dependent inhibitions were also tested. DDI potential was predicted according to the [I]/K ( i ) value. RESULTS: MPA was found to inhibit CYP2C9 and CYP3A4; half inhibition concentration (IC(50)) was 16.1 microM and 31.5 microM, respectively. Slight inhibition was observed on CYP1A2, CYP2A6, CYP2C8 and CYP2D6 with IC(50) of more than 100 microM. MPA exhibited activation rather than inhibition on CYP2E1. Further study revealed that MPA showed a noncompetitive inhibition on CYP2C9 and a competitive inhibition on CYP3A4 with K ( i ) of 9.0 microM and 36 microM, respectively. In addition, MPA was not a mechanism-based inhibitor to any of seven isoforms tested. By using predicted concentration of MPA in liver, [I]/K ( i ) was estimated to be 0.24 and 0.06 for CYP2C9 and CYP3A4, respectively. The concentration of phenytoin co-administrated with MPA was calculated to increase by 24%. CONCLUSION: Based on our results, MPA can possibly cause clinically relevant DDI via the inhibition of CYP2C9.

Adult↗
PubMed2006

Suppression of atherogenesis by delivery of TGFbeta1ACT using adeno-associated virus type 2 in LDLR knockout mice.

TGFbeta(1) deficiency has been attributed to the development of atherosclerosis. There is, however, little direct evidence for this concept. To examine this hypothesis, low-density lipoprotein receptor knockout (LDLR(-/-)) mice were injected via tail vein with recombinant adeno-associated virus type 2 (rAAV) carrying a bioactive TGFbeta(1) mutant (AAV/TGFbeta1ACT, n=10) or granulocyte-macrophage-colony stimulating factor (AAV/GM-CSF, n=10, a negative control) or saline (n=9, control), and then put on a high cholesterol diet. At 18 weeks, blood lipids were found to be similarly elevated in all LDLR(-/-) mice. TGFbeta1ACT and GM-CSF (DNA, mRNA, and protein) were highly expressed in the tissues of mice given TGFbeta1ACT or AAV/GM-CSF, respectively, showing sustained transfection following gene delivery by the systemic route. Saline-treated and AAV/GM-CSF-treated LDLR(-/-) mice showed extensive areas of atherosclerotic lesion formation. There was evidence of intense oxidative stress (nitrotyrosine staining), inflammation (CD68 staining), and expression of adhesion molecules and the ox-LDL receptor LOX-1 (gene array analysis) in the atherosclerotic tissues. Importantly, atherosclerotic lesion formation was markedly inhibited in the LDLR(-/-) mice given AAV/TGFbeta1ACT. Expression of adhesion molecules and LOX-1, oxidative stress, and inflammatory response all were inhibited in the mice given AAV/TGFbeta1ACT (P<0.05 vs. saline-treated or GM-CSF-treated LDLR(-/-) mice). These data for the first time demonstrate that systemic delivery of TGFbeta1ACT gene via AAV can inhibit formation of atherosclerotic lesions, possibly via anti-inflammatory and anti-oxidant mechanisms. These findings suggest a novel view of TGFbeta(1) in atherogenesis and a potential new gene therapy for treatment of atherosclerosis.

Adenoviridae↗
PubMed2006

Ginsenoside metabolites, rather than naturally occurring ginsenosides, lead to inhibition of human cytochrome P450 enzymes.

There is still an argument about ginseng-prescription drug interactions. To evaluate the influence on cytochrome P450 (P450) activities of ginseng in the present study, the influence on P450 activities of naturally occurring ginsenosides and their degradation products in human gut lumen was assayed by using human liver microsomes and cDNA-expressed CYP3A4. The results showed that the naturally occurring ginsenosides exhibited no inhibition or weak inhibition against human CYP3A4, CYP2D6, CYP2C9, CYP2A6, or CYP1A2 activities; however, their main intestinal metabolites demonstrated a wide range of inhibition of the P450-mediated metabolism. There was no mechanism-based inhibition found on these P450 isoforms. It is noteworthy that Compound K, protopanaxadiol (Ppd), and protopanaxatriol (Ppt) all exhibited moderate inhibition against CYP2C9 activity, and Ppd and Ppt also exhibited potent competitive inhibition against CYP3A4 activity. We suggest that after oral administration, naturally occurring ginsenosides might influence hepatic P450 activity in vivo via their intestinal metabolites.

Animals↗
PubMed2006

Mitochondrial and nuclear DNA damage induced by curcumin in human hepatoma G2 cells.

Curcumin is extensively used as a spice and pigment and has anticarcinogenic effects that could be linked to its antioxidant properties. However, some studies suggest that this natural compound possesses both pro- and antioxidative effects. In this study, we found that curcumin induced DNA damage to both the mitochondrial and nuclear genomes in human hepatoma G2 cells. Using quantitative polymerase chain reaction and immunocytochemistry staining of 8-hydroxydeoxyguanosine, we demonstrated that curcumin induced dose-dependent damage in both the mitochondrial and nuclear genomes and that the mitochondrial damage was more extensive. Nuclear DNA fragments were also evident in comet assays. The mechanism underlies the elevated level of reactive oxygen species and lipid peroxidation generated by curcumin. The lack of DNA damage at low doses suggested that low levels of curcumin does not induce DNA damage and may play an antioxidant role in carcinogenesis. But at high doses, we found that curcumin imposed oxidative stress and damaged DNA. These data reinforce the hypothesis that curcumin plays a conflicting dual role in carcinogenesis. Also, the extensive mitochondrial DNA damage might be an initial event triggering curcumin-induced cell death.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2006

Neuroprotective effects of ebselen are associated with the regulation of Bcl-2 and Bax proteins in cultured mouse cortical neurons.

There is little information available on the mechanisms underlying the neuroprotective actions of the organoselenium compound ebselen. In this study, we sought to determine the relationship between alterations in the expression of Bcl-2 and Bax proteins and intracellular levels of calcium and the protective effects of ebselen with a concentration range of 0.01-20 microM against glutamate toxicity in cultured mouse cortical neurons. Pretreatment with ebselen at moderate doses (4-12 microM), but not at lower or higher doses, significantly improved glutamate-induced suppression of cell viability. Pretreatment with ebselen (8 microM) also prevented apoptotic alterations, completely reversed the suppression of Bcl-2 expression, and significantly inhibited Bax overexpression, but did not alter elevated intracellular concentrations of calcium induced by glutamate. Pre-, co-, and post-treatment with ebselen (8 microM) had similar potency in improving the decreased viability of glutamate-exposed cells. These results indicate that the neuroprotective effects of ebselen at low doses are associated with the regulation of Bcl-2 and Bax proteins but appear to be independent of glutamate-mediated elevation of intracellular calcium, suggesting that different mechanisms are involved in the actions of low and high dose regimens. Ebselen may be an effective agent used for early treatment of acute brain injuries.

Analysis of Variance↗
PubMed2006

Molecular dissection of angiotensin II-activated human LOX-1 promoter.

OBJECTIVE: LOX-1, a receptor for oxidized low-density lipoprotein, plays a critical role in atherosclerosis. Its expression is upregulated by pro-atherogenic stimuli, such as angiotensin II (Ang II). In this study, we explored LOX-1 transcriptional promoter activation in response to Ang II in human coronary artery endothelial cells (HCAECs). METHODS AND RESULTS: We constructed full-length and deletion LOX-1 promoter mutants and examined their activation in response to Ang II in HCAECs. The Ang II (1 micromol/L for 24 hours) markedly induced LOX-1 promoter activity beyond the basal level, and a 116-bp fragment (between nt -2247 and -2131) was necessary for this induction. Within this 116-bp promoter fragment, there is a potential binding motif for transcription factor NF-kappaB. By EMSA, we observed the activation of NF-kappaB by Ang II. The critical role of NF-kappaB in Ang II-induced LOX-1 promoter activation was confirmed by mutagenesis assay, and further confirmed by blocking NF-kappaB activation with the NF-kappaB inhibitor caffeic acid phenethyl ester or NF-kappaB p65 siRNA. CONCLUSIONS: This study strongly suggests that Ang II, by activating NF-kappaB, induces LOX-1 promoter activation.

Angiotensin II↗
PubMed2006

Quasiclassical trajectory simulations of OH(v) + NO2 --> HONO2* --> OH(v') + NO2: capture and vibrational deactivation rate constants.

Quasiclassical trajectory calculations are used to investigate the dynamics of the OH(v) + NO(2) --> HONO(2) --> OH(v') + NO(2) recombination/dissociation reaction on an analytic potential energy surface (PES) that gives good agreement with the known structure and vibrational frequencies of nitric acid. The calculated recombination rate constants depend only weakly on temperature and on the initial vibrational energy level of OH(v). The magnitude of the recombination rate constant is sensitive to the potential function describing the newly formed bond and to the switching functions in the PES that attenuate inter-mode interactions at long range. The lifetime of the nascent excited HONO(2) depends strongly not only on its internal energy but also on the identity of the initial state, in disagreement with statistical theory. This disagreement is probably due to the effects of slow intramolecular vibrational energy redistribution (IVR) from the initially excited OH stretching mode. The vibrational energy distribution of product OH(v') radicals is different from statistical distributions, a result consistent with the effects of slow IVR. Nonetheless, the trajectory results predict that vibrational deactivation of OH(v) via the HONO(2) transient complex is approximately 90% efficient, almost independent of initial OH(v) vibrational level, in qualitative agreement with recent experiments. Tests are also carried out using the HONO(2) PES, but assuming the weaker O-O bond strength found in HOONO (peroxynitrous acid). In this case, the predicted vibrational deactivation efficiencies are significantly lower and depend strongly on the initial vibrational state of OH(v), in disagreement with experiments. This disagreement suggests that the actual HOONO PES may contain more inter-mode coupling than found in the present model PES, which is based on HONO(2). For nitric acid, the measured vibrational deactivation rate constant is a useful proxy for the recombination rate, but IVR randomization of energy is not complete, suggesting that the efficacy of the proxy method must be evaluated on a case-by-case basis.

Journal Article↗
PubMed2006

Identification of a Zn2+-binding site on the dopamine D2 receptor.

Zinc (II) modulates the function of many integral membrane proteins. To identify the Zn(2+)-binding site responsible for allosteric modulation of the D(2) dopamine receptor, we first demonstrated that the binding site is likely located in extracellular loops or in transmembrane regions that are accessible from the extracellular milieu. We mutated every histidine in these regions to alanine; two mutants, H394A and H399A, exhibited a reduced response to Zn(2+). Combined mutation of H394 and H399 caused a larger effect of zinc than did either single mutation. Mutation of other potential Zn(2+)-binding residues predicted to be in proximity to H394 or H399 did not substantially alter the potency of Zn(2+). The double mutant H394A/H399A was similar to D(2) in affinity for [(3)H]spiperone and ability to inhibit cyclic AMP accumulation. We conclude that binding of Zn(2+) to H394 and H399 on the dopamine D(2) receptor contributes to allosteric regulation of antagonist binding.

Amino Acid Substitution↗
PubMed2006

Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) transcriptional regulation by Oct-1 in human endothelial cells: implications for atherosclerosis.

LOX-1, a receptor for ox-LDL (oxidized low-density lipoprotein), has recently been determined to play a critical role in the progression of atherosclerosis. LOX-1 expression (mRNA and protein) has been shown to be up-regulated by pro-atherogenic stimuli, such as ox-LDL and Ang II (angiotensin II). However, the molecular mechanisms of these up-regulations are unclear. In the present study, we explored LOX-1 transcriptional promoter activation in response to ox-LDL and Ang II. Under basal states, LOX-1 core promoter (LOX-1 -35/+36) was found to be sufficient for its basal activity in HCAECs (human coronary artery endothelial cells). More importantly, we found that ox-LDL (60 microg/ml for 24 h) induced LOX-1 promoter activity significantly and that a 105 bp fragment (between nt -1599 and -1494) was required for this activation. Within this 106 bp fragment, there is a potential binding motif for the transcription factor Oct-1 (octamer-1). By electrophoretic mobility-shift assay, we observed the activation of Oct-1 by ox-LDL. The critical role of Oct-1 in ox-LDL-induced LOX-1 promoter activation was further confirmed by mutagenesis assay. For comparison, we also examined LOX-1 promoter activation in response to Ang II (1 micromol/l for 24 h). Interestingly, another promoter region, between nt -2336 and -1990, was required for Ang II-induced LOX-1 promoter activation. In conclusion, the present study strongly suggests that ox-LDL, by activating Oct-1, induces LOX-1 promoter activation. Furthermore, this study suggests that while ox-LDL and Ang II both induce LOX-1 expression in HCAECs, the underlying mechanisms of promoter activation are different from each other.

Angiotensin II↗
PubMed2006

Germinal vesicle chromatin configurations of bovine oocytes.

A common feature in the configuration of germinal vesicle (GV) chromatin in most species is that diffuse chromatin condenses into a perinucleolar ring during follicular growth; however, no such ring was observed in goat oocytes. Reports on whether bovine GV chromatin condenses into a perinucleolar ring are controversial. Besides, it is not known whether the perinucleolar ring in an oocyte represents a step toward final maturation or atresia. Changes in GV chromatin configurations during growth and maturation of bovine oocytes were studied using a new method that allows a clearer visualization of both the nucleolus and the chromatin after Hoechst and chromomycin A(3) staining. On the basis of the degree of condensation and distribution, the GV chromatin of bovine oocytes were classified into five configurations: NSN with diffuse chromatin in the whole nuclear area, N with condensed netlike chromatin, C with clumped chromatin, SN with clumped chromatin surrounding the nucleoli, and F with floccular chromatin near the nucleoli and near the nuclear envelope. Most of the oocytes were at the NSN stage in the <1.4-mm follicles, but the NSN pattern disappeared completely in follicles larger than 1.5mm. The SN pattern began to emerge in 1.5-mm follicles, and the number of SN oocytes increased while the number of oocytes with N and C configurations decreased with follicular growth. During maturation in vivo, while the number of N, C, and SN oocytes decreased, that of the F oocytes increased and reached maximum at 51h post prostaglandin injection. After that, the number of F oocytes decreased significantly because of germinal vesicle breakdown (GVBD). During maturation in vitro, GV chromatin configurations changed in a similar manner as during maturation in vivo. Fewer oocytes were at N, C, and SN stages, but more were at F and GVBD stages in the atretic than in the healthy follicles. Serum starvation slowed the F-GVBD transition of the in vitro maturing oocytes. More oocytes were of the SN or C configuration when ovaries were transported at 45-40 degrees C than at 35-30 degrees C. Most of the heated oocytes were blocked at the SN stage during in vitro maturation. It is concluded that (i) bovine GV chromatin condenses into a perinucleolar ring during follicular growth; (ii) bovine oocytes were synchronized at the F stage before GVBD; (iii) oocyte GV chromatin configurations were affected by serum starvation, high temperature, and follicular atresia.

Animals↗
PubMed2006

A RGD-containing oligopeptide (K)16GRGDSPC: a novel vector for integrin-mediated targeted gene delivery.

A 23 amino acid, bifunctional integrin-targeted synthetic oligopeptide was evaluated for ex vivo gene delivery to rabbit bone marrow stromal cells (BMSCs). Synthesis of the peptide (K)16GRGDSPC was performed on a solid-phase batch peptide synthesizer. BMSCs were transfected with plasmid DNA coding for luciferase by (K)16GRGDSPC and the transfection efficiency was assayed. The influences of chloroquine and polyethyleneimine on the transfection efficiency were also examined. The target specificity of (K)16GRGDSPC to mediate exogenous gene into BMSCs was analyzed using cell attachment test and gene delivery inhibition test. The results showed that the transfection efficiency of the oligopeptide vector was lower than that of Lipofectamine. But in the presence of endosomal buffer chloroquine or endosomal disrupting agent polyethyleneimine, the transfection efficiency of the vector was greatly enhanced. In addition, RGD-containing peptides inhibited BMSCs' attachment to the 96-well plates pretreated with fibronectin or vitronectin and significantly decreased the transfection efficiency of the oligopeptide vector. These studies demonstrated that oligopeptide (K)16GRGDSPC was an ideal novel targeted non-viral gene delivery vector, which was easy to be synthesized, high efficient and low cytotoxicity. The vector could effectively deliver exogenous gene into rat BMSCs.

Animals↗
PubMed2006

Influence of ginsenoside Rh1 and F1 on human cytochrome p450 enzymes.

For an oral herbal medicine, the components that can enter the systemic circulation may be the really effective components. In the present study, the effects on the human cytochrome P450 activities of ginsenoside Rb (1) and two hydrolysis products of 20( S)-protopanaxatriol ginsenosides in humans, namely ginsenoside Rh (1) and F (1), which may reach the systemic circulation after oral administration of ginseng extract, were evaluated. Our results showed that Rb (1) exhibited no marked effects on the activities of human cytochrome P450, whereas Rh (1) and F (1) exhibited competitive inhibition of the activity of CYP3A4 with K(i) values of 57.7 +/- 9.6 microM and 67.8 +/- 16.2 microM, respectively. F (1) also exhibited a weaker inhibition of the activity of CYP2D6. Rh (1) exhibited a weak stimulation rather than an inhibition of the activity of CYP2E1. The degradation of ginsenosides in the gastrointestinal tract may play an important role in the ginseng-associated drug-drug interactions, but the effects might be not due to Rh (1) and F (1).

Adult↗
PubMed2006

Gambogic acid and epigambogic acid, C-2 epimers with novel anticancer effects from Garcinia hanburyi.

Gambogic acid, usually isolated as an inseparable stereomeric mixture of C-2 epimers, was newly separated into two epimers (1 and 2) from the gamboges of Garcinia hanburyi. The stereochemistry at C-2 was clearly defined by extensive spectroscopic analysis and direct comparison of NMR and HPLC data with those of the known R-epimer. Both epimers were examined for their cytotoxicities against human leukemia K562 (K562/S) and doxorubicin-resistant K562 (K562/R) cell lines. Different from doxorubicin (IC (50) = 10.78 microM for K562/R and 0.66 microM for K562/S), epimers 1 and 2 exhibited similar activities against both cell lines (IC(50) = 1.32 and 0.89 microM for 1, IC(50) = 1.11 and 0.86 microM for 2). These results suggested that both epimers were not multidrug resistance (MDR) substrates. Furthermore, epimers 1 and 2 were tested for their inhibitory effects against six human cytochrome P-450 enzymes. Epimers 1 and 2 showed little inhibitory effects toward five of the enzymes except CYP2C9. Interestingly, when tested against CYP2C9, S-epimer 2 had an inhibitory effect 20-fold stronger than that of R-epimer 1.

Antineoplastic Agents, Phytogenic↗
PubMed2006

Of the major phenolic acids formed during human microbial fermentation of tea, citrus, and soy flavonoid supplements, only 3,4-dihydroxyphenylacetic acid has antiproliferative activity.

Dietary flavonoids are poorly absorbed from the gastrointestinal tract. Colonic bacteria convert flavonoids into smaller phenolic acids (PA), which can be absorbed into the circulation and may contribute to the chemopreventive activity of the parent compounds. The purpose of our study was to determine whether flavonoids from green and black tea (GT, BT), citrus fruit with rutin (CF+R) and soy (S) supplements exposed to the same conditions in a dynamic in vitro model of the colon (TIM-2) will form the same phenolic acid products of microbial metabolism. About 600 mg of flavonoids from GT, BT, CF+R and S extracts were infused at t = 0 and 12 h into the TIM-2. Samples from the lumen and dialysate were collected at t = 0,4,8,12,16,24 and 28h. The flavonoid and PA concentrations were measured by HPLC and GC-MS. GT, BT, and CF+R formed 3-methoxy-4-hydroxyphenylacetic acid (3M4HPAA), 4-hydroxyphenyl acetic acid (4HPAA), 3,4-dihydroxyphenylacetic acid (3,4DHPAA), and 3-(3-hydroxyphenyl) propionic acid (3,3HPPA). BT flavonoids were also metabolized to 2,4,6-trihydroxybenzoic acid (2,4,6THBA) and CF+R flavonoids to 3-(4-hydroxy-3-methoxyphenyl) propionic acid (3,4H3MPPA), 3-hydroxyphenyl acetic acid (3HPAA) and a small amount of hippuric acid. After S infusion, we found 3M4HPAA and 4HPAA only. Among these phenolic acids, only 3,4DHPAA exhibited antiproliferative activity in prostate and colon cancer cells. 3,4DHPAA was significantly (P < 0.005) more inhibitory in colon cancer cells (HCT116) compared with an immortalized normal intestinal epithelial cell line (IEC6). In summary, fermentation by intestinal microbes of GT, BT, C+R, and S flavonoids resulted in the conversion to the same major phenolic acids.

3,4-Dihydroxyphenylacetic Acid↗