Copyright © 2008 Elsevier Inc. All rights reserved.
Original Contribution
Isoliquiritigenin induces monocytic differentiation of HL-60 cells
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Defang Lia, 1, Zhenhua Wanga, 1, Hongmei Chena, Jingying Wangb, Qiusheng Zhenga, 
, 
, Jing Shangc, , and Ji Lia, b
aKey Laboratory of Xinjiang Endemic Phytomedicine Resources, Ministry of Education, School of Pharmacy, Shihezi University, Shihezi 832002, China
bDepartment of Pharmaceutical Sciences, Center for Cardiovascular Research and Alternative Medicine, University of Wyoming School of Pharmacy, Laramie, WY 82071, USA
cNational Drug Screening Laboratory, China Pharmaceutical University, Nanjing 210009, China
Received 9 September 2008;
revised 29 October 2008;
accepted 10 November 2008.
Available online 3 December 2008.
Abstract
It has been proven that 
isoliquiritigenin
could inhibit the proliferation of some kinds of cancer cell lines and has a strong antioxidative activity. The purpose of this study is to investigate whether the antioxidant isoliquiritigenin 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 cell proliferentiation and survival. The morphological changes, nitroblue tetrazolium chloride (NBT) reductive activity, and the CD11b and CD14 surface antigens were used as the biomarkers of redifferentiation of HL-60 cells. 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 and decreased the iROS levels in a dose-dependent manner, while the treatment did not increase the lethality rate. After 72 h treatment with 10 μg/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, P < 0.01) and CD14 (20.4 ± 2.30 vs 2.63 ± 0.133, P < 0.01) cells increased significantly. The NBT reductive activity increased 2.3-fold as compared to that of the control group. As an antioxidant, ISL decreased the iROS formation in a dose-dependent manner. All the results indicate that the antioxidant ISL is able to induce the monocytic differentiation in leukemia cells. ISL has the potential as a drug to cure leukemia with fewer side effects.
Keywords: Isoliquiritigenin; HL-60 cells; Differentiation; Antioxidant
Abbreviations: MTT, The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium; NBT, nitroblue tetrazolium chloride; DCFH-DA, 2,7-dichlorodihydrofluorescein diacetate; iROS, intracellular reactive oxygen species; ATRA, all-trans retinoic acid; APL, acute promyelocytic leukemia; AML, acute myelocytic leukemia; DMSO, dimethyl sulfoxide; ISL, isoliquiritigenin
