Indoleacetic Acid Falcarindiol Ester Induces Granulocytic Differentiation of the Human Leukemia Cell Line HL-60

 

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Abstract

Indoleacetic acid falcarindiol ester (compound 1) has previously been isolated and purified using an SiO₂ column and ODS HPLC from an acetone extract of Japanese ivy (Hedera rhombea). Here we investigate the differentiation-inducing activity of compound 1 using the human promyelocytic leukemia HL-60 cell line. The effect of compound 1 on HL-60 cell viability and proliferation was determined at different treatment times using the 3-(4,5-dimethythiazol-2-yl)-2,5-diohenyl-2H-tetrazolium bromide (MTT) assay and flow cytometry analysis. Also cell cycle kinetics were examined using propidium iodide staining of DNA. Cell differentiation was assessed by specific and non-specific esterase double staining assays, and by detection of the cell surface differentiation markers CD11b and CD14 using flow cytometry. The results showed HL-60 cell growth inhibition at 0.1 and 1.0 μg/mL compound 1, whereas 10 μg/mL was cytotoxic. The growth suppression induced by compound 1 was accompanied by G₀/G₁ phase arrest in the cell cycle at 1.0 μg/mL. Moreover, staining and immunochemical analysis indicated that compound 1 induced granulocytic differentiation in HL-60 cells. This is the first report describing granulocytic differentiation activity of a falcarindiol derived polyacetylenic compound on leukemia cells.

References

• 1 Christensen L, Brandt K. Bioactive polyacetylenes in food plants of the Apiaceae family: occurrence, bioactivity and analysis.  J Pharm Biomed Anal. 2006;  41 683-93
  CrossrefPubMedGoogle Scholar
• 2 Zidorn C, Johrer K, Ganzera M, Schubert B, Sigmund E M, Mader J. et al . Polyacetylenes from the Apiaceae vegetables carrot, celery, fennel, parsley, and parsnip and their cytotoxic activites.  J Agric Food Chem. 2005;  53 2518-23
  CrossrefPubMedGoogle Scholar
• 3 Lim Y J, Lee C O, Hong J, Kim D, Im K S, Jung J H. Cytotoxic polyacetylenic alcohols from the marine sponge Petrosia species.  J Nat Prod. 2001;  64 565-7
  PubMedGoogle Scholar
• 4 Sohn J, Lee C, Chung D, Park S, Kim I, Hwang W. Effect of petroleum ether extract of Panax ginseng roots on proliferation and cell cycle progression of human renal cell carcinoma cells.  Exp Mol Med. 1998;  30 47-51
  PubMedGoogle Scholar
• 5 Aoki S h, Matsui K, Takada T, Hong W, Kobayashi M. Lembehyne A, a spongean polyacetylene, induces neuronal differentiation in neuroblastoma cell.  Biochem Biophys Res Commun. 2001;  289 558-63
  CrossrefPubMedGoogle Scholar
• 6 Yamazaki M, Hirakura K, Miyaichi Y, Imakura K, Kita M, Chiba K. et al . Effect of polyacetylenes on the neurite outgrowth of neuronal culture cells and scopolamine-induced memory impairment in mice.  Biol Pharm Bull. 2001;  24 1434-6
  CrossrefPubMedGoogle Scholar
• 7 Wang N, Yao X, Ishii R, Kitanaka S. Antiallergic agents from natural sources. 3. Structures and inhibitory effects on nitric oxide production and histamine release of five novel polyacetylene glucosides from Bidens parviflora Willd.  Chem Pharm Bull. 2001;  49 938-42
  CrossrefPubMedGoogle Scholar
• 8 Yamazoe S, Hasegawa K, Shigemori H. Growth inhibitory indole acetic acid polyacetylenic ester from Japanese ivy (Hedera rhombea Bean).  Phytochemistry. 2007;  68 1706-11
  CrossrefPubMedGoogle Scholar
• 9 Kwon B M, Lee S H, Kim K S, Lee I R, Lee U C, Hong S H. et al . Rhombenone: farnesyl protein transferase inhibitor from the leaves of Hedera rhombea Bean.  Bioorg Med Chem Lett. 1997;  7 971-4
  CrossrefPubMedGoogle Scholar
• 10 Fan Y, Chang H, He Y, Liu J, Zhao L, Yang D. et al . Thymopentin (TP5), an immunomodulatory peptide, suppresses proliferation and induces differentiation in HL-60 cells.  Biochim Biophys Acta. 2006;  1763 1059-66
  PubMedGoogle Scholar
• 11 Kim J S, Cho E W, Chung H W, Kim I G. Effects of tiron, 4,5-dihydroxy-1,3-benzenedisulfonic acid, on human promyelotic HL-60 leukemia cell differentiation and death.  Toxicology. 2006;  233 36-45
  PubMedGoogle Scholar
• 12 Isoda H, Shinmoto H, Kitamoto D, Matsumura M, Nakahara T. Differentiation of human promyelocytic leukemia cell line HL-60 by microbial extracellular glycolipids.  Lipids. 1997;  32 263-71
  CrossrefPubMedGoogle Scholar
• 13 Kuo H, Kuo W, Lee Y, Wang C, Tseng T. Enhancement of caffeic acid phenethyl ester on all-trans retinoic acid-induced differentiation in human leukemia HL-60 cells.  Toxicol Appl Pharmacol. 2006;  216 80-8
  CrossrefPubMedGoogle Scholar
• 14 James S Y, Williams M A, Newland A C, Colston K W. Leukemia cell differentiation: cellular and molecular interactions of retinoids and vitamin D.  Gen Pharmacol. 1999;  32 143-54.
  CrossrefPubMedGoogle Scholar
• 15 Tsiftsoglou A S, Pappas1 I S, Vizirianakis I S. Mechanisms involved in the induced differentiation of leukemia cells.  Pharmacol Ther. 2003;  100 257-90
  CrossrefPubMedGoogle Scholar
• 16 Honma Y, Akimoto M. Therapeutic strategy using phenotypic modulation of cancer cells by differentiation-inducing agents.  Cancer Sci. 2007;  98 643-51
  PubMedGoogle Scholar
• 17 Montenegro R C, Vasconcellos M C, Bezerra A S, Neto M A, Pessoa C, Moraes M O. et al . Pisosterol induces monocytic differentiation in HL-60 cells.  Toxicol In Vitro. 2007;  21 795-800
  CrossrefPubMedGoogle Scholar
• 18 Rossiter S, Folkes L K, Wardman P. Halogenated indol-3-acetic acids as oxidatively activated prodrugs with potential for targeted cancer therapy.  Bioorg Med Chem Lett. 2002;  12 2523-6
  CrossrefPubMedGoogle Scholar
• 19 Young J, Duthie S, Milne L, Christensen L, Duthie G, Bestwick C. Biphasic effect of falcarinol on Caco-2 cell proliferation, DNA damage, and apoptosis.  J Agric Food Chem. 2007;  55 618-23
  CrossrefPubMedGoogle Scholar

Prof. Dr. Hiroko Isoda

Graduate School of Life and Environmental Sciences

University of Tsukuba

1-1-1 Tennodai

Tsukuba

Ibaraki 305–8572

Japan

Phone: +81-29-853-5775

Fax: +81-29-853-5776

Email: isoda@sakura.cc.tsukuba.ac.jp