Yuh-Fang Chang

Quercetin Induces Oxidative Stress and Potentiates the Apoptotic Action of 2-Methoxyestradiol in Human Hepatoma Cells

Hepatocellular carcinoma (HCC) is the leading cause of cancer mortality in Asia. This study evaluated the growth inhibition effect of quercetin and 2-methoxyestradiol in vitro in human HCC cell lines. Combination treatment enhanced the cytotoxic effect in HA22T/VGH and HepG2 cell lines as compared with quercetin or 2-methoxyestradiol alone. The cell population of sub-G0/G1 phase and the level of annexin V binding were increased synergistically after combination treatment with quercetin and 2-methoxyestradiol in both cell lines. Moreover, quercetin combined with 2-methoxyestradiol increased superoxide levels, mitochondrial superoxide dismutase (MnSOD) in mRNA, protein levels, and SOD activity. Finally, we also found the mitochondrial membrane potential was decreased after combination treatment. The changes of reactive oxygen species and mitochondrial disruption were likely to be involved in the mechanism for the synergistic cytotoxicity effects of combination treatment in human hepatoma cells. These results provided a basis for further study of the potential usage of quercetin combination with hormonal agents for the treatment of human hepatoma.

Reactive Oxygen Species Production Is Involved in Quercetin-Induced Apoptosis in Human Hepatoma Cells

Abstract: Hepatocellular carcinoma (HCC) is the leading cause of cancer mortality in Asia. The aim of this study was to examine whether reactive oxygen species production is involved in quercetin-induced apoptosis in human HCC cell lines. Quercetin inhibited the growth of hepatoma cells in dose and time dependent manners. Quercetin treatment of hepatoma cells resulted in changes of cell cycle progression. The G0/G1phase was decreased and S phase was increased in HA22T/VGH cells after treatment with quercetin. The levels of apoptotic sub-G0/G1, reactive oxygen species and annexin V were increased prior to cell death and concurrent with lipid peroxidation in two human hepatoma cells after treatment with quercetin. Quercetin also enhanced the apoptotic effect of the chemotherapeutic agent, paclitaxel, in HA22T/VGH cells. Quercetin has therapeutic potential as an anti-cancer drug. These results provide basis for further study into the potential use of quercetin in combination with paclitaxel for treatment of hepatoma.

Steroid hormone receptors in three human gastric cancer cell lines.

Steroid hormone receptors in three human gastric adenocarcinoma cell lines and their transplanted tumors (except nontumorigenic KATO-III) in nude mice were determined by dextran-coated charcoal assay. Progesterone receptors (PgR) were found in all cell lines, transplanted NUGC-3, and AZ 521 tumors. Estrogen receptors (ER) were found in KATO-III cells, transplanted NUGC-3, and AZ 521 tumors, whereas glucocorticoid receptors (GR) were found only in NUGC-3 tumor and no androgen receptor was found in any cell lines or transplanted tumors. Since NUGC-3 cells had ER, PgR, and GR, it was used for the study of the effects of steroid hormones on growth. The results showed the cell cycle phase distributions and growth rate of transplanted tumors were similar in hormone-treated and nontreated groups. The persistent expression of PgR in gastric cancer cell lines and tumors, and the slight increase of tumor volumes in the progesterone-treated group suggests that progesterone and its receptors may be important in the pathogenesis of gastric cancer, but their biological function remains to be elucidated.

Dimethyladamantylmaleimide-induced in vitro and in vivo growth inhibition of human colon cancer Colo205 cells.

The effect of N-1-(3,5-dimethyladamantyl)maleimide (DMAMI) on the growth of Colo205 human colon cancer cells was examined both in vitro and in vivo. Flow cytometry analysis showed a decrease of G2/M Colo205 cells at 4–6 h after treatment with DMAMI prior to accumulation of apoptotic cells at 24 h. Significant changes in cell morphology, i.e. shrinkage and chromatin condensation of cells, were observed after treatment with DMAMI. In the analysis of the apoptosis markers, it was found that the increase of Annexin V binding to membrane, peroxide radicals, dissipation of the mitochondrial membrane potential, and the activation of caspase-3, -8 and -9 were all evident at 4–6 h after treatment with DMAMI. In vivo analysis showed that treatment of Colo205 tumor-bearing SCID mice with DMAMI (230 mg/kg, intratumoral, once) resulted in rapid tumor damage that leads to significant tumor growth inhibition and no obvious acute toxicity. These results suggest that DMAMI has potential for local treatment of cancer.

Analysis of monoamines in the cerebrospinal fluid of Chinese patients with Alzheimer's disease.

We have established HPLC assay conditions that could measure the levels of 14 monoamines and their metabolites simultaneously. Monoamine levels in cerebrospinal fluids of 12 Chinese patients with Alzheimers disease were compared with those in samples from patients with benign prostate hyperplasia. Of the 14 monoamines and metabolites, only three were found to be present in all samples. Although the levels of 5-hydroxy-3-indoleacetic acid (HIAA) and homovanillic acid (HVA) in cerebrospinal fluid of patients with Alzheimers disease were lower, and the levels of 3-methoxy-4-hydroxyphenylglycol (MHPG) higher, as compared to control patients, no significant differences were found between these two groups.

Simultaneous Determination of Fourteen Catecholamines and Their Metabolites by High Performance Liquid Chromatography with Electrochemical Detection

Abstract A simple method has been developed for simultaneous determination of 14 catecholamines and their metabolites in cerebrospinal fluid and brain tissue by reversed-phase, ion-pair high-performance liquid chromatography with electrochemical detection. The time required for complete separation and analysis of all compounds was less than 35 min. Quantitation was based on the use of an internal standard isoproterenol. The mobile phase consisted of a 91:9 (v/v) mixture of 0.1 M formic acid and acetonitrile containing sodium-1-octane sulfonic acid. Using this method, analysis of neurotransmitters in brain tissue can be accomplished without a clean-up procedure.