Qing-Yi Wei

Antioxidant-based lead discovery for cancer chemoprevention: the case of resveratrol.

Resveratrol is a well-known natural antioxidant and cancer chemopreventive agent that has attracted much interest in the past decade. Resveratrol-directed compounds were synthesized, and their antioxidant effects against reactive oxygen species (ROS)-induced DNA damage, their prooxidant effects on DNA damage in the presence cupric ions, and their cytotoxic and apoptosis-inducing effects on human promyelocytic leukemia (HL-60) cells were investigated in vitro. It was found that the compounds bearing o-diphenoxyl groups exhibited remarkably higher activities in inhibiting ROS-induced DNA damage, accelerating DNA damage in the presence cupric ions, and inducing apoptosis of HL-60 cells compared with the ones bearing no such groups. The detail mechanism of the structure-activity relationship was also studied by the oxidative product analysis of resveratrol and its analogues with galvinoxyl radical or cupric ions and UV-visible spectra change in the presence cupric ions. This study reveals a good and interesting correlation between antioxidant and prooxidant activity, as well as cytotoxicity and apoptosis-inducing activity against HL-60 cells, and provides an idea for designing antioxidant-based cancer chemoprevention agents.

Iridoid glucosides from Chinese herb Lonicera chrysatha and their antitumor activity

A new bis-iridoid glucosides, secologanin methyl hemiacetal-yl-6′-secologanin dimethyl acetal (chrysathain, 1), was isolated from the methanol extract of the leaves of Chinese medicinal plant Lonicera chrysatha along with nine known iridoid glucosides, i.e., loganin (2), secologanin (3), secologanin dimethylacetal (4), 8-epi-kingiside (5) 7α-morroniside (6), 7β-morroniside (7), vogeloside (8) 7-epi-vogeloside (9) and sarracenin (10). Their structures were elucidated by spectroscopic methods. Compounds 1–5 showed moderate in vitro antitumour activity against human promyelocytic leukemia (HL-60) cells.

Synthesis of 1,1,2-triphenylethylenes and their antiproliferative effect on human cancer cell lines.

Tamoxifen analogs (1–3) and 1,1,2-triphenylethylenes (4–7) have been synthesized by the McMurry coupling reaction. Their antiproliferative effects on MCF-7 human breast-cancer cells, HO-8910 human ovarian-carcinoma cells, and (HL)-60 human promyelocytic-leukemia cells were studied by use of the colorimetric MTT assay or sulphorhodamine B assay. Compounds 2 and 3 exhibited significantly higher antiproliferative activity on all the three cell lines, and compound 6 exhibited a remarkably higher antiproliferative activity on HO-8910 and human peripheral blood HL-60 cell lines, than did tamoxifen. Structure–activity relationship analysis demonstrates that the methoxyl group on the 2-phenyl ring contributes critically to the activity.

Redifferentiation of human hepatoma cells induced by green tea polyphenols

A novel approach for the treatment of cancer is the differentiation therapy in which cancer cells are induced to attain a mature phenotype when exposed to differentiation inducers. To examine the effects of polyphenols extracted from green tea, i.e. ( – )-epicatechin (EC), ( – )-epigallocatechin (EGC), ( – )-epicatechin gallate (ECG) and ( – )-epigallocatechin gallate (EGCG), on the proliferation and redifferentiation of human hepatoma cell line SMMC-7721, we measured the changes of cell growth, cell surface charge and cell morphography after treament with green tea polyphenols. It was found that the growth curve of treated cells was decreased remarkably, cell surface charge of treated cells was decreased and the microvilli on the surface of treated cells were reduced obviously. It confirmed that green tea polyphenols could reverse malignant phenotypic characteristics and induced redifferentiation of SMMC-7721 cells. The ability of green tea polyphenols to inhibit reactive oxygen species (ROS)-mediated oxidative damage of DNA was also assessedin vitro by measuring the conversion of supercoiled pBR322 plasmid DNA to the open circular and linear forms. It was found that green tea polyphenols could significantly inhibit the oxidative damage of DNA induced by a water-soluble azo initiator 2,2′-azobis(2-amidinopropane hydrochloride) (AAPH). However, they could promote the oxidative damage of DNA induced by H2O2 and Fe2+ at high concentrations. The relationship between the anti-cancer activity and antioxidation-prooxidation activity of green tea polyphenols is discussed.