Biomedical subjects

C W Chi

Publications and source records attributed to C W Chi.

At least 19 recordsLinked to original sources

PubMed2005

Cholinesterase inhibitor affects the amyloid precursor protein isoforms in patients with Alzheimer's disease.

An altered platelet ratio of amyloid precursor protein (APP) isoforms might be a diagnostic, predictive, or therapeutic marker for Alzheimer's disease (AD). Our purpose was to test the hypothesis that this ratio might serve as a therapeutic marker for AD patients treated with the cholinesterase inhibitor, galantamine. Thirty-nine patients (mean age 76.6 +/- 9.4 years) with AD were treated with galantamine for 12 weeks. Patients were evaluated at baseline, 4 and 12 weeks by cognitive testing along with a determination of their platelet APP isoform ratio. Western blotting was performed to calculate the APP isoform ratio. At the end of the treatment, cognitive scores significantly improved, and the ratio of the high-molecular-weight (130 kDa) isoform to the low-molecular-weight (110-106 kDa) isoforms increased. These results suggest that cholinesterase inhibition might be involved in APP processing.

Aged↗

PubMed2005

Effects of 1, 6-Bis[4-(4-amino-3-hydroxyphenoxy)phenyl]diamantane (DPD), a reactive oxygen species and apoptosis inducing agent, on human leukemia cells in vitro and in vivo.

1, 6-Bis[4-(4-amino-3-hydroxyphenoxy)phenyl]diamantine (DPD), a new cytostatic and differentiation inducing agent, was found to inhibit the growth of several cancer cell lines in the National Cancer Institute (NCI) Anticancer Drug Screen system. Previously, we demonstrated that DPD inhibited the growth of human colon cancer cell lines both in vitro and in vivo. In this study, we examined the anticancer effects of DPD on two human leukemia cells lines. DPD exerted growth inhibitory activities in vitro against two human leukemia cell lines, the promyeloid line HL-60 and the lymphoblastic line Molt-3. The in vivo effect of tumor growth suppression by DPD was also observed in mouse xenografts. No acute toxicity was observed after an intra-peritoneal challenge of DPD in "severe combined immune-deficiency" (SCID) mice twice a week. The in vitro study showed HL-60 was more sensitive to DPD than Molt-3 through induction of G(0)/G(1) cell-cycle arrest with the appearance of a hypodiploid DNA fraction. The increased superoxide (O(2)(-)), dissipation of the mitochondrial membrane potential, activation of caspase 3, and increase in annexin V binding were evident before apoptosis in DPD-treated cells. The superoxide dismutase 1 (SOD1) mRNA expression was also decreased in DPD-treated HL-60 and Molt-3 cells. Thus, it appeared that inhibition of SOD might be the major cause for the production of cellular superoxide with concomitant decrease of H(2)O(2) in DPD-treated cells. Addition of antioxidant can reduce DPD-induced mitochondrial damage, caspase activation, and annexin V binding in HL-60 cells. The results suggest that the cellular generation of O(2)(-) plays a role in initiating and coordinating DPD-mediated growth arrest and apoptosis of HL-60 cells. Importantly, addition of arsenic trioxide, a compound capable of reactive oxygen species (ROS) generation, significantly enhanced the in vitro activity of DPD. These results suggest that DPD appears to be a potential new modality in human leukemia therapy.

Adamantane↗

PubMed2004

Estrogen-metabolizing gene COMT polymorphism synergistic APOE epsilon4 allele increases the risk of Alzheimer disease.

Alzheimer disease (AD) is a polygenic multifactorial disorder. Several studies suggested that the neuroprotective effect of estrogen was based on an APOE-dependent mechanism. The goals of the current study were to determine if the genes involved in estrogen metabolism were linked to the risk of AD and find out if there was an interaction between estrogen-metabolizing gene polymorphisms and the APOE epsilon4 allele in the risk of prevalent AD. We investigated 66 patients with AD and 86 age- and gender-matched normal subjects. The polymorphisms of APOE and estrogen-metabolizing genes CYP17, CYP1A1 and COMT were examined. No association was found between each estrogen-metabolizing gene polymorphism and AD. However, the COMT HH genotype and APOE epsilon4 allele had a synergistic effect on the risk of AD. Taking subjects with epsilon4-epsilon4-/HH- as reference, the risk of developing AD in subjects with one epsilon4 allele (epsilon4+epsilon4-/HH-) was 2.6 (95% confidence interval, CI, 0.7- 9.1); however, the risk in subjects with both HH and one epsilon4 (epsilon4+epsilon4-/HH+) increased to 3.6 (95% CI 1.2-10.6). The subjects with homozygous epsilon4 still had the highest risk in developing AD (odds ratio 6.6, 95% CI 0.6-69.6). The p value of the linear trend test for this regression model was 0.004. It is possible that a high metabolism of estrogen by COMT may have reduced the protective effect of estrogen in AD. Further studies to clarify this interaction may improve our understanding of the generic risks for AD.

Aged↗

PubMed2004

ApoE epsilon4 allele is associated with incidental hallucinations and delusions in patients with AD.

Of 135 patients with Alzheimer disease (AD), 56 without psychiatric symptoms at the first visit were followed for a mean period of 51.9 +/- 10.3 months to identify incident psychiatric symptoms. The hazard ratios of ApoE epsilon4 allele in developing psychiatric symptoms were calculated by Cox regression hazard analyses. The presence of the ApoE epsilon4 allele carried a 19.0-fold risk for developing hallucinations and a 3.4-fold risk for delusions.

Aged↗

PubMed2004

Alteration of the copy number and deletion of mitochondrial DNA in human hepatocellular carcinoma.

Somatic mutations in mitochondrial DNA (mtDNA) have been detected in hepatocellular carcinoma (HCC). However, it remains unclear whether mtDNA copy number and mitochondrial biogenesis are altered in HCC. In this study, we found that mtDNA copy number and the content of mitochondrial respiratory proteins were reduced in HCCs as compared with the corresponding non-tumorous livers. MtDNA copy number was significantly reduced in female HCC but not in male HCC. Expression of the peroxisome proliferator-activated receptor gamma coactivator-1 was significantly repressed in HCCs (P<0.005), while the expression of the mitochondrial single-strand DNA-binding protein was upregulated, indicating that the regulation of mitochondria biogenesis is disturbed in HCC. Moreover, 22% of HCCs carried a somatic mutation in the mtDNA D-loop region. The non-tumorous liver of the HCC patients with a long-term alcohol-drinking history contained reduced mtDNA copy number (P<0.05) and higher level of the 4977 bp-deleted mtDNA (P<0.05) as compared with non-alcohol patients. Our results suggest that reduced mtDNA copy number, impaired mitochondrial biogenesis and somatic mutations in mtDNA are important events during carcinogenesis of HCC, and the differential alterations in mtDNA of male and female HCC may contribute to the differences in the clinical manifestation between female and male HCC patients.

Alcohol Drinking↗

PubMed2003

Study of in vitro and in vivo effects of 1,6-Bis[4-(4-amino-3-hydroxyphenoxy)phenyl]diamantane (DPD), a novel cytostatic and differentiation inducing agent, on human colon cancer cells.

A diamantane derivative 1,6-Bis [4-(4-amino-3-hydroxyphenoxy) phenyl] diamantane (DPD) was found to inhibit the growth of several cancer cell lines in the National Cancer Institute (NCI) Anticancer Drug Screen system. In this study, we examined the in vitro and in vivo effects of DPD on human colon cancer cells. DPD exerted growth inhibitory activities in vitro against three human colon cancer cell lines (Colo 205, HT-29, and HCT-15). DPD-treated cells were arrested at G(0)/G(1) as analysed by flow cytometric analysis. The expression of cyclin D was decreased in DPD-treated cells. The differentiation markers of carcinoembryonic antigen and fibronectin were significantly increased in colon cancer cells after treatment with DPD. The epithelium-like brush borders on HT-29 cell surface were also demonstrated at 1 week after withdrawal from DPD treatment. The DPD-induced cell growth inhibition and differentiation were irreversible after removal of DPD. The in vivo effect of tumour growth suppression by DPD was also observed in mouse xenografts. No acute toxicity was observed after an intraperitoneal challenge of DPD in BALB/c-nude mice weekly. These results suggest that DPD appears to be a new potentially less toxic modality of cancer therapy.

Adamantane↗

PubMed2001

2-Methoxyestradiol-induced caspase-3 activation and apoptosis occurs through G(2)/M arrest dependent and independent pathways in gastric carcinoma cells.

BACKGROUND: 2-Methoxyestradiol (2-Me), one of the estrogen metabolites, has recently been found to possess anti-angiogenesis activity in vivo. Many chemotherapeutic agents, such as taxol, docetaxel, and vinblastine, interact with microtubules and then induce apoptosis. It has been suggested that 2-Me acts on microtubules and results in G(2)/M-cycle arrest of tumor cells. Whether 2-Me induces apoptosis in gastric carcinoma cell lines is not known. Moreover, reactive oxygen species (ROS) produced by 2-Me may be involved in cytotoxicity of tumor cells. Thus, another objective of this study was to evaluate the relation between cell cycle arrest, ROS formation, and caspase activity levels after 2-Me treatment in gastric carcinoma cells. METHODS: It was determined whether 2-Me directly induced apoptosis in two gastric carcinoma cell lines (SC-M1 and NUGC-3) through caspase-3 and caspase-8 activation and, eventually, induced DNA fragmentation. To clarify the effect of 2-Me-induced G(2)/M arrest in apoptosis, calcium ionophore, A23187, and thapsigargin were used to modulate 2-Me-induced cell cycle responses. Moreover, the role of 2-Me-induced ROS formation in the cell cycle responses also was evaluated. RESULTS: It was found that 2-Me treatment resulted in G(2)/M-cycle arrest, caspase-8 and caspase-3 activation, and DNA fragmentation. In addition, the 2-Me induced, concomitant increases of peroxide and superoxide anions were correlated with G(2)/M-cycle arrest. Treatment with calcium ionophore A23187 and thapsigargin partially reversed the 2-Me-induced G(2)/M-cycle arrest, with a concomitant decrease in both peroxide and superoxide levels. Moreover, A23187 blocked the 2-Me-induced caspase-3 activation, whereas thapsigargin had no effect. Treatment with calcium channel blockers did not affect 2-Me-induced cell cycle arrest or caspase-3 activation. CONCLUSIONS: These results suggest that the 2-Me-induced apoptosis of gastric carcinoma cells by DNA fragmentation accompanied caspase activation. Elevation of free radicals was associated with G(2)/M-cycle arrest. The induction of G(2)/M-cycle arrest is not a prerequisite for caspase activation.

2-Methoxyestradiol↗

PubMed2001

A genome-wide study of microsatellite instability in advanced gastric carcinoma.

BACKGROUND: Microsatellite instability (MSI) has been described in many human carcinomas, including gastric carcinomas (GCs). There are inconsistent findings regarding the association of MSI with various subsets of GC with specific clinicopathologic features. The objective of this study was to define MSI in advanced GC at a genome-wide level and to evaluate the clinical relevance of MSI in these patients. METHODS: Forty-one gastric adenocarcinomas with serosa invasion (T3) were analyzed at 59 loci that detected at least one site per arm of each autosome in human genome. The expression patterns of mismatch repair proteins hMLH1 and hMSH2 were examined by immunohistochemistry. Comparisons were made by categorizing tumors into three groups: tumors with MSI at multiple loci (at more than three loci), tumors with MSI at low level (at one to three loci), and microsatellite-stable (MSS) tumors. Clinical significance of MSI in advanced GC was evaluated. The relative rates of hypermutability of the 59 markers also were determined. RESULTS: A significant association was found between tumors with MSI at multiple loci and the expanding type of tumor growth by Ming's histologic classification (P = 0.001), whereas tumors with MSI at low level and MSS tumors are clinicopathologically indistinguishable. The 59 dinucleotide repeat markers displayed varying degrees of susceptibility toward genetic instability. The relative rates of hypermutability of these markers were consistent with a normal distribution pattern in which the frequency of unstable tumors detected at different chromosomal loci varied from 0% to 20%. CONCLUSIONS: The authors' results showed that advanced GC with MSI at multiple loci progress preferentially in an expanding mode, supporting the notion that high MSI tumors and low MSI/MSS tumors evolve through different genetic pathways. Thus, microsatellite testing may have clinical utility as a favorable prognostic marker.

Adaptor Proteins, Signal Transducing↗

PubMed2001

Accumulation of mitochondrial DNA deletions in human oral tissues -- effects of betel quid chewing and oral cancer.

Accumulation of mitochondrial DNA (mtDNA) mutations in human tissues has been associated with intrinsic aging and environmental insult. Recently, mtDNA mutations have been detected in various tumors, including head and neck tumors. However, the factors affecting the occurrence and accumulation of mtDNA deletions in tumor tissues are poorly understood. In Taiwan, betel quid chewing is a major risk factor for oral cancer. Using polymerase chain reaction (PCR) techniques, we examined large-scale deletions of mtDNA in 53 pairs of tumor and non-tumor oral tissues from the patients with or without betel quid chewing history. The results revealed that irrespective of the history of betel quid chewing, the incidences of the 4977bp deletion and other deletions of mtDNA were lower in the tumor portion as compared with the non-tumor portion. The average proportions of the 4977bp deleted mtDNA in the tumor tissues of the betel quid chewers and non-betel quid chewers were 13- and 5-fold, respectively, lower than those in the corresponding non-tumor tissues. Moreover, the average proportion of 4977bp deleted mtDNA was significantly higher (P<0.05) in the non-tumor oral tissues of the patients with betel quid chewing history than that of the patients without the history of betel quid chewing. These results suggest that betel quid chewing may increase mtDNA mutation in human oral tissues and that accumulation of mtDNA deletions and subsequent cytoplasmic segregation of these mutations during cell division could be an important contributor to the early phase of oral carcinogenesis.

Areca↗

PubMed2001

Human Ca2+/calmodulin-dependent protein kinase kinase beta gene encodes multiple isoforms that display distinct kinase activity.

Ca(+2)/calmodulin-dependent protein kinases (CaMKs) are activated upon binding of Ca(+2)/calmodulin. To gain maximal activity, CaMK I and CaMK IV can be further phosphorylated by an upstream kinase, CaMK kinase (CaMKK). We previously isolated cDNA clones encoding human CaMKK beta isoforms that are heterogeneous in their 3'-sequences (Hsu, L.-S., Tsou, A.-P., Chi, C.-W., Lee, C.-H., and Chen, J.-Y. (1998) J. Biomed. Sci. 5, 141-149). In the present study, we examined the genomic organization and transcription of the human CaMKK beta gene. The human CaMKK beta locus spans more than 40 kilobase pairs and maps to chromosome 12q24.2. It is organized into 18 exons and 17 introns that are flanked by typical splice donor and acceptor sequences. Two major species of transcripts, namely the beta1 (5.6 kilobase pairs) and beta2 (2.9 kilobase pairs), are generated through differential usage of polyadenylation sites located in the last and penultimate exons. Additional forms of CaMKK beta transcripts were also identified that resulted from alternative splicing of the internal exons 14 and/or 16. These isoforms display differential expression patterns in human tissues and tumor-derived cell lines. They also exhibit a distinct ability to undergo autophosphorylation and to phosphorylate the downstream kinases CaMK I and CaMK IV. The differential expression of CaMKK beta isoforms with distinct activity further suggests the complexity of the regulation of the CaMKK/CaMK cascade and an important role for CaMKK in the action of Ca(+2)-mediated cellular responses.

Amino Acid Sequence↗

PubMed2001

Molecular characterization of an anti-epilepsy peptide from the scorpion Buthus martensi Karsch.

For a long time Asian scorpion Buthus martensi Karsch (BmK) has been used in Chinese traditional medicine to cure many diseases of nervous system. Here we report the purification and characterization of a pharmacologically active neurotoxin from the scorpion BmK. This toxin had little toxicity in mice and insects but was found to have an anti-epilepsy effect in rats, and is thus named as BmK anti-epilepsy peptide (BmK AEP). Its amino-acid sequence was determined by lysylendopeptidase digestion, Edman degradation and mass spectrographic analysis. Based on the determined sequence, the gene coding for this peptide was also cloned and sequenced by the 3' and 5' RACE methods. It encodes a precursor of 85 amino-acid residues including a signal peptide of 21 residues, a mature peptide of 61 residues and three additional residues Gly-Lys-Lys at the C-terminus. The additional Gly sometimes followed by one or two basic residues is prerequisite for the amidation of its C-terminus. C-terminal amidation was also verified by the molecular-mass determination of BmK AEP. This anti-epilepsy peptide toxin shares homology with other depressant insect toxins. The remarkable difference between them was mainly focused at residues 6, 7 and 39; these residues might relate to the unique action of BmK AEP.

Amino Acid Sequence↗

PubMed2001

Association analysis of the 5-HT6 receptor polymorphism C267T with depression in patients with Alzheimer's disease.

A significant increase of 267C allele of the 5-HT(6) receptor gene has been reported in patients with Alzheimer's disease (AD). Because a deficit in serotonergic neurotransmission is involved in major depression, we tried to find out whether 267C allele is associated with depressive disorders in AD. A psychiatrist interviewed all AD patients and their caregivers for evidence of depression using a Chinese version of the Standard Clinical Interview for DSM-III-R. The difference in the 5-HT(6) genotype or allele distributions between the AD patients with depressive disorders (n = 25) and those without (n = 120) was not significant.

Aged↗

PubMed2001

Nonsteroidal anti-inflammatory drugs for treatment of advanced gastric cancer: cyclooxygenase-2 is involved in hepatocyte growth factor mediated tumor development and progression.

Surgical treatment of gastric cancer patients is dismal because advanced tumor is often noted at diagnosis. In order to obtain better adjuvant therapy for gastric cancer patients after operation, it is important to understand the mechanism of invasion and metastasis. It is well known that binding of hepatocyte growth factor (HGF) to its receptor (c-Met) regulates gastric cancer progression and metastasis. Recently, HGF was found to up-regulate the expression of cyclooxygenase-2 (COX-2) gene and increase prostaglandin (PG)synthesis in gastric mucosa cells. Over-expression of COX-2 and increased PG secretion have also been found to be involved in the growth and metastasis of gastric cancer. These results together suggest that the signaling pathway of HGF and c-Met may be mediated through ERK2 activation, up-regulation of COX-2 and increased production of PGE(2)in gastric cancer cells. In view of the fact that c-Met is over-expressed in the majority of gastric cancer patients with poor prognosis, COX-2 specific inhibitors may provide beneficial effects in these patients.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2001

Immunohistochemical studies of Na+/I- symporter in human thyroid tissues--a correlation with clinical thyroid scintigraphy.

BACKGROUND: Thyroid Na+/I- symporter (NIS) is thought to play an important role in iodide uptake in thyrocytes. We hypothesize that there is correlation between the expression of NIS protein in the normal and diseased thyroid tissues and their clinical thyroid scintigraphy. METHODS: Twenty-seven patients, aged from 21 to 81, were studied from the surgical department of a tertiary referral center. Ten patients were with papillary carcinoma, 5 with follicular carcinoma, 5 with follicular adenoma, 5 with nodular goiter and 2 with Graves' disease. All the carcinoma patients underwent total thyroidectomy while others had lobectomy or subtotal thyroidectomy. The thyroid tissue sections prepared for study were stained with polyclonal hNIS antibody (SS Chiang, Ohio). RESULTS: Most of the nodular goiters were negatively stained except 2 samples that showed weak signal focally. All cases with follicular adenoma or follicular carcinoma were negative for NIS expression, while some with papillary carcinoma were stained positive at sporadic follicles with weak signal. The thyroid tissue of Graves' disease was stained positive for NIS expression. CONCLUSIONS: Thyroid tissues with hypofunctioning nodules displayed significantly reduced or undetectable level of NIS expression. It correlated well with pre-operative thyroid scans.

Adult↗

PubMed2001

The Inhibitory Activities of Recombinant Eglin C Mutants on Kexin and Furin, Using Site-directed Mutagenesis and Molecular Modeling.

Mammalian furin and yeast kexin are members of the proprotein convertase family involved in the proteolytic processing of many important precursor proteins. Here the gene coding for the subtilisin inhibitor eglin C was totally synthesized and expressed in E.coli. Substitution of residues at each position P(1), P(2) and P(4) of eglin C with a basic residue using protein engineering could make eglin C a very strong inhibitor for furin (K(i) around 10(-9) mol/L),and even more strong for kexin (K( i ) around 10(-11) mol/ L). Results indicated that (1) A basic residue Lys or Arg at P(1) site is prerequisite for the inhibitor. (2) The second mutation with basic residue at P(4) site drastically increase the inhibitory activity by two orders of magnitude. (3) A basic residue at P(2) site is favorable for the binding to the enzyme, but unfavorable for the stability of the inhibitor, resulting in a temporary inhibition. (4) A hydrophobic residue is preferential at P(3) site. Based on the known crystal structures of subtilisin and eglin C, the interaction between the enzyme and inhibitor was modeled, and their involved residues were predicted which gave a good explanation to the experimental results.

Journal Article↗

PubMed2000

The neuroprotective effects of phytoestrogens on amyloid beta protein-induced toxicity are mediated by abrogating the activation of caspase cascade in rat cortical neurons.

Amyloid beta protein (Abeta) elicits a toxic effect on neurons in vitro and in vivo. In present study we attempt to elucidate the mechanism by which Abeta confers its neurotoxicity. The neuroprotective effects of phytoestrogens on Abeta-mediated toxicity were also investigated. Cortical neurons treated with 5 microm Abeta-(25-35) for 40 h decreased the cell viability by 45.5 +/- 4.6% concomitant with the appearance of apoptotic morphology. 50 microm kaempferol and apigenin decreased the Abeta-induced cell death by 81.5 +/- 9.4% and 49.2 +/- 9.9%, respectively. Abeta increased the activity of caspase 3 by 10.6-fold and to a lesser extent for caspase 2, 8, and 9. The Abeta-induced activation of caspase 3 and release of cytochrome c showed a biphasic pattern. Apigenin abrogated Abeta-induced cytochrome c release, and the activation of caspase cascade. Kaempferol showed a similar effect but to a less extent. Kaempferol was also capable of eliminating Abeta-induced accumulation of reactive oxygen species. These two events accounted for the remarkable effect of kaempferol on neuroprotection. Quercetin and probucol did not affect the Abeta-mediated neurotoxicity. However, they potentiated the protective effect of apigenin. Therefore, these results demonstrate that Abeta elicited activation of caspase cascades and reactive oxygen species accumulation, thereby causing neuronal death. The blockade of caspase activation conferred the major neuroprotective effect of phytoestrogens. The antioxidative activity of phytoestrogens also modulated their neuroprotective effects on Abeta-mediated toxicity.

Amyloid beta-Peptides↗

PubMed2000

Comparison of 2-methoxyestradiol-induced, docetaxel-induced, and paclitaxel-induced apoptosis in hepatoma cells and its correlation with reactive oxygen species.

BACKGROUND: Previously, the authors observed that paclitaxel treatment of hepatoma cells resulted in differential cytotoxicity. Whether other antimicrotubule agents (docetaxel and 2-methoxyestradiol) are more effective than paclitaxel is not clear. Moreover, whether the modulation of reactive oxygen species (ROS) is involved in the drug-induced growth inhibition of hepatoma cells is not known. METHODS: The authors examined the effects of 2-methoxyestradiol, paclitaxel, and docetaxel on HepG2, Hep3B, HA22T/VGH, and Hepa1-6 hepatoma cell lines. The parameters examined included cell viability, cell membrane permeability, cell cycle distribution, DNA fragmentation, and ROS generation. RESULTS: Docetaxel and paclitaxel inhibited the growth of hepatoma cells at submicromolar concentrations, whereas that of 2-methoxyestradiol was within a micromolar range. This drug-induced growth inhibition was cell cycle dependent. 2-Methoxyestradiol-treated (10-50 microM) cells resulted in G2/M block prior to apoptosis. High dose (0.1 microM) docetaxel- and paclitaxel-treated cells resulted in a G2/M arrest followed by generation of polyploidy or apoptosis; however, low dose (0.01 microM) treatment induced apoptosis without G2/M arrest. The low dose effect was more significant in docetaxel-treated cells than in paclitaxel-treated cells. Although these antimicrotubule agents increased the formation of ROS, antioxidant treatment did not block drug-induced cell cycle and growth inhibition effects. CONCLUSIONS: The current results suggest that the growth inhibition of hepatoma cells induced by 2-methoxyestradiol, paclitaxel, and docetaxel was mediated through G2/M-phase arrest, caspase activation, and DNA fragmentation. The drug-induced apoptosis was independent of ROS formation. Docetaxel was more effective than paclitaxel in killing hepatoma cells. The potential of using 2-methoxyestradiol and docetaxel for the treatment of patients with hepatoma is worthy of further study.

2-Methoxyestradiol↗

PubMed2000

Enhanced hydroxychavicol-induced cytotoxic effects in glutathione-depleted HepG2 cells.

Hydroxychavicol (HC) is the major safrole urinary metabolite in rats and humans. The cytotoxic potential of HC in metabolically competent cells has yet to be studied. HC alone was slightly toxic to HepG2 cells. However, the cytotoxicity increased significantly (P<0.05) when HepG2 cells were pretreated with buthionine sulfoximine (BSO), suggesting that endogenous glutathione participates in HC-induced cytotoxicity. Addition of catalase or N-acetylcysteine prevented the BSO plus HC-mediated cytotoxicity. HC also increased 8-hydroxy-2'-deoxyguanosine formation and apoptosis in BSO-pretreated HepG2 cells and this increase could also be suppressed by catalase. These data suggest that BSO pretreatment enhanced HC-induced cytotoxic effects in HepG2 cells, which are related to oxidative DNA damage.

8-Hydroxy-2'-Deoxyguanosine↗