Planta Med 2009; 75(10): 1134-1140
DOI: 10.1055/s-0029-1185479
Pharmacology
Original Paper
© Georg Thieme Verlag KG Stuttgart · New York

Cytotoxic Activity of Isoliquiritigenin towards CCRF‐CEM Leukemia Cells and its Effect on DNA Damage

Yuangang Zu1 , Xia Liu1 , Yujie Fu1 , Xiaoguang Shi1 , Nan Wu1 , Liping Yao1 , Thomas Efferth2
  • 1Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin, P. R. China
  • 2German Cancer Research Center, Heidelberg, Germany
Further Information

Publication History

received Dec. 10, 2008 revised February 1, 2009

accepted February 9, 2009

Publication Date:
16 March 2009 (online)

Abstract

The cytotoxic activity of isoliquiritigenin (ISL) towards CCRF‐CEM human T-cell leukemia cells and DNA damage induction were investigated in the present study. The anti-proliferative effect of ISL on CCRF‐CEM cell line in vitro was analyzed. In order to further explore the underlying mechanism of cell growth inhibition of ISL towards CCRF‐CEM cell line, the cell cycle distribution and mitochondrial membrane potential (ΔΨm) disruption were measured. ISL exerted significant activity towards CCRF‐CEM cells. The growth inhibitory ratio was concentration- and time-dependent with an IC50 value of 18.38 µM. The cell cycle was arrested in the G2/M phase upon treatment with low doses of ISL. Mitochondrial membrane potential (ΔΨm) disruption was observed at low ISL doses. The effect of ISL on DNA damage was analyzed by agarose gel electrophoresis and atomic force microscopy (AFM). Either ISL or Cu2+ failed to cause pBR322 DNA damage. However, plasmid DNA was damaged after treatment with ISL in the presence of Cu2+. Two forms of plasmid DNA closed circular and linear forms were visualized by AFM.

References

  • 1 Yamazaki S, Morita T, Endo H, Hamamoto T, Baba M, Joichi Y, Kaneko S, Okada Y, Okuyama T, Nishino H, Tokue A. Isoliquiritigenin suppresses pulmonary metastasis of mouse renal cell carcinoma.  Cancer Lett. 2002;  183 23-30
  • 2 Kumar S, Sharma A, Madan B, Singhal V, Ghosh B. Isoliquiritigenin inhibits IkB kinase activity and ROS generation to block TNF‐a induced expression of cell adhesion molecules on human endothelial cells.  Biochem Pharmacol. 2007;  73 1602-1612
  • 3 Hsu Y L, Kuo P L, Lin C C. Isoliquiritigenin induces apoptosis and cell cycle arrest through p 53-dependent pathway in Hep G2 cells.  Life Sci. 2005;  77 279-292
  • 4 Haraguchi H, Ishikawa H, Mizutani K, Tamura Y, Kinoshita T. Antioxidative and superoxide scavenging activities of retrochalcones in Glycyrrhiza inflate.  Bioorg Med Chem. 1998;  6 339-347
  • 5 Fotsis T, Pepper M S, Aktas E, Breit S, Rasku S, Adlercreutz H, Wähälä K, Montesano R, Schweigerer L. Flavonoids, dietary-derived inhibitors of cell proliferation and in vitro angiogenesis.  Cancer Res. 1997;  57 2916-2921
  • 6 Carlson B, Lahusen T, Singh S, Loaiza-Perez A, Worland P J, Pestell R, Albanese C, Sausville E A, Senderowicz A M. Down-regulation of cyclin D1 by transcriptional repression in MCF‐7 human breast carcinoma cells induced by flavopiridol.  Cancer Res. 1999;  59 4634-4641
  • 7 Tawata M, Aida K, Noguchi T, Ozaki Y, Kume S, Sasaki H, Chin M, Onaya T. Anti-platelet action of isoliquiritigenin, an aldose reductase inhibitor in licorice.  Eur J Pharmacol. 1992;  212 87-92
  • 8 Wegener J W, Nawrath H. Cardiac effects of isoliquiritigenin.  Eur J Pharmacol. 1997;  326 37-44
  • 9 Jung J I, Lim S S, Choi H J, Cho H J, Shin H K, Kim E J, Chung W Y, Park K K, Park J H. Isoliquiritigenin induces apoptosis by depolarizing mitochondrial membranes in prostate cancer cells.  J Nutr Biochem. 2006;  17 689-696
  • 10 Kanazawa M, Satomi Y, Mizutani Y, Ukimura O, Kawauchi A, Sakai T, Baba M, Okuyama T, Nishino H, Miki T. Isoliquiritigenin inhibits the growth of prostate cancer.  Eur Urol. 2003;  43 580-586
  • 11 Yamazaki S, Morita T, Endo H, Hamamoto T, Baba M, Joichi Y, Kaneko S, Okada Y, Okuyama T, Nishino H, Tokue A. Isoliquiritigenin suppresses pulmonary metastasis of mouse renal cell carcinoma.  Cancer Lett. 2002;  183 23-30
  • 12 Ii T, Satomi Y, Katoh D, Shimada J, Baba M, Okuyama T, Nishino H, Kitamura N. Induction of cell cycle arrest and p 21CIP1/WAF1 expression in human lung cancer cells by isoliquiritigenin.  Cancer Lett. 2004;  207 27-35
  • 13 Chen C J, Hsu M H, Huang L J, Yamori T, Chung J G, Lee F Y, Teng C M, Kuo S C. Anticancer mechanisms of YC‐1 in human lung cancer cellline, NCI-H226.  Biochem Pharmacol. 2008;  75 360-368
  • 14 Ma J, Fu N Y, Pang D B, Wu W Y, Xu A L. Apoptosis induced by isoliquiritigenin in human gastric cancer MGC‐803 cells.  Planta Med. 2001;  67 754-757
  • 15 Efferth T, Davey M, Olbrich A, Rücker G, Gebhart E, Davey R. Activity of drugs from traditional Chinese medicine toward sensitive and MDR1- or MRP1-overexpressing multidrug-resistant human CCRF‐CEM leukemia cells.  Blood Cell Mol Dis. 2002;  28 160-168
  • 16 Chowdhury S A, Kishino K, Satoh R, Hashimoto K, Kikuchi H, Nishikawa H, Shirataki Y, Sakagami H. Tumor-specificity and apoptosis-inducing activity of stilbenes and flavonoids.  Anticancer Res. 2005;  25 2055-2063
  • 17 Pogozelski W K, Tullius T D. Oxidative strand scission of nucleic acids: routes initiated by hydrogen abstraction from the sugar moiety.  Chem Rev. 1998;  98 1089-1107
  • 18 Cardozo-Pelaez F, Brooks P J, Stedeford T, Song S, Sanchez-Ramos J. DNA damage, repair, and antioxidant systems in brain regions: a correlative study.  Free Radic Biol Med. 2000;  28 779-785
  • 19 Zhang Q, Pan J, Zhao C, Wang Y, Jia Z, Zheng R. Non-enzymatic fast repair of DNA oxidative damage might also exist in cells.  Cell Biol Int. 2008;  32 654-662
  • 20 Wang T, Chen L X, Long Y, Wu W M, Wang R. DNA damage induced by caffeic acid phenyl ester in the presence of Cu(II) ions: Potential mechanism of its anticancer properties.  Cancer Lett. 2008;  263 77-88
  • 21 Sakano K, Kawanishi S. Metal-mediated DNA damage induced by curcumin in the presence of human cytochrome P450 isozymes.  Arch Biochem Biophys. 2002;  405 223-230
  • 22 Cao J, Liu Y, Jia L, Zhou H M, Kong Y, Yang G, Jiang L P, Li Q J, Zhong L F. Curcumin induces apoptosis through mitochondrial hyperpolarization and mtDNA damage in human hepatoma G2 cells.  Free Radic Biol Med. 2007;  43 968-975
  • 23 Sun Y L, Zhong W J. Curcumin-induced oxidative damage of plasmid DNA.  Environ Occup Med. 2006;  23 31-33
  • 24 Hansma H G, Kasuya K, Oroudjev E. Atomic force microscopy imaging and pulling of nucleic acids.  Curr Opin Struct Biol. 2004;  14 380-385
  • 25 Shlyakhtenko L S, Gall A A, Filonov A, Cerovac Z, Lushnikov A, Lyubchenko Y L. Silatrane-based surface chemistry for immobilization of DNA, protein-DNA complexes and other biological materials.  Ultramicroscopy. 2003;  97 279-287
  • 26 Cai Y J, Wei Q Y, Fang J G, Yang L, Liu Z L, Wyche J H, Han Z. The 3,4-dihydroxyl groups are important for trans-resveratrol, analogs to exhibit enhanced antioxidant and apoptotic activities.  Anticancer Res. 2004;  24 999-1002
  • 27 Sabzevari O, Galati G, Moridani M Y, Siraki A, O'Brien P J. Molecular cytotoxic mechanisms of anticancer hydroxychalcones.  Chem Biol Interact. 2004;  148 57-67
  • 28 Azmi A S, Bhat S H, Hanif S, Hadi S M. Plant polyphenols mobilize endogenous copper in human peripheral lymphocytes leading to oxidative DNA breakage: a putative mechanism for anticancer properties.  FEBS Lett. 2006;  580 533-538
  • 29 Kastan M B, Bartek J. Cell-cycle checkpoints and cancer.  Nature. 2004;  432 316-323
  • 30 Speit G, Hochsattel R, Vogel W. The contribution of DNA single-strand breaks to the formation of chromosome aberrations and SCEs.  Basic Life Sci. 1984;  29 229-244
  • 31 Zheng L F, Dai F, Zhou B, Yang L, Liu Z L. Prooxidant activity of hydroxycinnamic acids on DNA damage in the presence of Cu(II) ions: mechanism and structure–activity relationship.  Food Chem Toxicol. 2008;  46 149-156
  • 32 Taskov H, Dimitrova E, Serbinova M, Mendisova L, Bobev D. Immunological subtypes of childhood acute lymphoblastic leukemia in Bulgaria.  Leuk Res. 1995;  19 877-881
  • 33 Bene M C, Castoldi G, Knapp W, Ludwig W D, Matutes E, Orfao A, van't Veer M B. Proposals for the immunological classification of acute leukemias. European Group for the Immunological Characterization of Leukemias (EGIL).  Leukemia. 1995;  9 1783-1786
  • 34 Dartsch D C, Schaefer A, Boldt S, Kolch W, Marquardt H. Comparison of anthracycline-induced death of human leukemia cells: programmed cell death versus necrosis.  Apoptosis. 2002;  7 537-548
  • 35 Min D J, Moskowitz N P, Brownstein C, Lee H, Horton T M, Carroll W L. Diverse pathways mediate chemotherapy-induced cell death in acute lymphoblastic leukemia cell lines.  Apoptosis. 2006;  11 1977-1986

Prof. Yujie Fu

Key Laboratory of Forest Plant Ecology
Ministry of Education
Northeast Forestry University

Harbin 150040

People's Republic of China

Fax: + 86 4 51 82 19 05 35

Email: yujie_fu2002@yahoo.com

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