It has been proven that isoliquiritigenin could inhibit the proliferation of some kinds of cancer cell lines andhas a strong antioxidative activity. The purpose of this study is to investigate whether the antioxidantisoliquiritigenin affects the proliferation and redifferentiation in HL-60 cells. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) colorimetric method and trypan blue staining were used to measure cellproliferentiation and survival. The morphological changes, nitroblue tetrazolium chloride (NBT) reductiveactivity, and the CD11b and CD14 surface antigens were used as the biomarkers of redifferentiation of HL-60cells. The intracellular reactive oxygen species (iROS) level was detected by a fluorescent probe, 2,7-dichlorodihydrofluorescein diacetate (DCFH-DA). Isoliquiritigenin (ISL) inhibited the cell proliferation anddecreased the iROS levels in a dose-dependent manner, while the treatment did not increase the lethalityrate. After 72 h treatment with 10μg/ml ISL, a typical differentiated morphology was observed in HL-60 cells,including the decrease of karyoplasmic ratio and the increase of kidney-shape nuclear cells. The positive rate(%) of CD11b (26.4±3.90 vs 7.70±1.04, Pb0.01) and CD14 (20.4±2.30 vs 2.63±0.133, Pb0.01) cells increasedsignificantly. The NBT reductive activity increased 2.3-fold as compared to that of the control group. As anantioxidant, ISL decreased the iROS formation in a dose-dependent manner. All the results indicate that theantioxidant ISL is able to induce the monocytic differentiation in leukemia cells. ISL has the potential as adrug to cure leukemia with fewer side effects.

Because both c-Src and iNOS are key regulatory enzymes in tumorigenesis, a new series of 4-heterocycleamine-3-quinolinecarbonitriles as potent dual inhibitors of both enzymes were designed, synthesizedand evaluated as multiple targets agents in cancer therapy. All compounds were evaluated by two relatedenzyme inhibition assays and an anti-proliferation assay in vitro. The results showed that most compoundsinhibited c-Src and iNOS well. The best compound 8 inhibited both enzymes with the IC50 valuesof 34.8 nM and 26.7 lM. Several compounds also showed moderate anti-proliferation at 10 lM againstcolon and liver cancer cell lines.

Because both c-Src and iNOS are key regulatory enzymes in tumorigenesis, a new series of 4-heteroarylamino-3-quinolinecarbonitriles as potent dual inhibitors of both enzymes were designed, prepared, and evaluated for blocking multiple signaling pathways in cancer therapy. All compounds were evaluated by two related enzyme inhibition assays and an anti-proliferation assay in vitro. The results showed that most compounds could inhibit both enzymes, and several of them showed potent inhibition activity against different cancer cell lines. The best compound 20 (CPU-Y020) showed the IC50 values of 6.58 and 7.61 lM toward colon cancer HT-29 and liver cancer HepG2 cell lines.