Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Open Life Sciences

formerly Central European Journal of Biology

Editor-in-Chief: Ratajczak, Mariusz

IMPACT FACTOR 2018: 0.504
5-year IMPACT FACTOR: 0.583

CiteScore 2018: 0.63

SCImago Journal Rank (SJR) 2018: 0.266
Source Normalized Impact per Paper (SNIP) 2018: 0.311

ICV 2017: 154.48

Open Access
See all formats and pricing
More options …
Volume 4, Issue 3


Volume 10 (2015)

The influence of Trisenox on actin organization in HL-60 cells

Magdalena Izdebska
  • Department of Histology and Embryology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, 85-092, Bydgoszcz, Poland
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Dariusz Grzanka
  • Department of Clinical Pathomorphology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, 85-094, Bydgoszcz, Poland
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Lidia Gackowska
  • Department of Immunology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, 85-094, Bydgoszcz, Poland
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Agnieszka Żuryń
  • Department of Histology and Embryology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, 85-092, Bydgoszcz, Poland
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Alina Grzanka
  • Department of Histology and Embryology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, 85-092, Bydgoszcz, Poland
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2009-07-26 | DOI: https://doi.org/10.2478/s11535-009-0021-5


The aim of this study was to show the influence of Trisenox (arsenic trioxide, ATO) on cytoplasmic and nuclear F-actin organization in HL-60 human leukemia cell line. Changes in localization were determined with the use of fluorescence microscopy and flow cytometry. Alterations, in both cytoplasmic and nuclear actin, were observed in cells exposed to ATO. F-actin network underwent accumulation and formed aggregates, that were very often placed under the cell membrane in whole cells and at the periphery of isolated nuclei. Addition of ATO also induced apoptosis and a decrease in G2 phase cells. These results suggest the influence of actin on the formation of apoptotic bodies and also participation of this protein in apoptotic alterations within nuclei, i.e. chromatin reorganization.

Keywords: F-actin; HL-60; Trisenox (arsenic trioxide, ATO); Apoptosis; Fluorescence; Flow cytometry

  • [1] Zhu J., Okumura H., Ohtake S., Nakamura S., Nakao S., Arsenic trioxide induces apoptosis in leukemia/lymphoma cell lines via the CD95/CD95L system, Oncol. Rep., 2003, 10, 705–770 Google Scholar

  • [2] Waxman S., Anderson K.C., History of the development of arsenic derivatives in cancer therapy, Oncologist, 2001, 6, 3–10 http://dx.doi.org/10.1634/theoncologist.6-suppl_2-3CrossrefGoogle Scholar

  • [3] Chen G.Q., Zhu J., Shi X.G., Ni J.H., Zhong H.J., Si G.Y., et al., In vitro studies on cellular and molecular mechanisms of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia: As2O3 induces NB4 cells apoptosis with downregulation of Bcl-2 expression and modulation of PML-RAR alpha/PML proteins, Blood, 1996, 88, 1052–1061 Google Scholar

  • [4] Soignet S.L., Maslak P., Wang Z.G., Jhanwar S., Calleja E., Dardashti L.J., et al., Complete remission after treatment of acute promyelocytic leukemia with arsenic trioxide, N. Engl. J. Med., 1998, 339, 1341–1348 http://dx.doi.org/10.1056/NEJM199811053391901CrossrefGoogle Scholar

  • [5] Tarkanyi I., Dudognon C., Hillion J., Pendino F., Lanotte M., Aradi J., et al., Retinoid/arsenic combination therapy of promyelocytic leukemia: induction of telomerase-dependent cell death, Leukemia, 2005, 19, 1806–1811 http://dx.doi.org/10.1038/sj.leu.2403923CrossrefGoogle Scholar

  • [6] Germolec D.R., Spalding J., Yu H.S., Chen G.S., Simeonova P.P., Humble M.C., et al., Arsenic enhancement of skin neoplasia by chronic stimulation of growth factors, Am. J. Pathol., 1998, 153, 1775–1785 Google Scholar

  • [7] Grad J.M., Bahlis N.J., Reis I., Oshiro M.M., Dalton W.S., Boise L.H., Ascorbic acid enhances arsenic trioxide-induced cytotoxicity in multiple myeloma cells, Blood, 2001, 98, 805–813 http://dx.doi.org/10.1182/blood.V98.3.805CrossrefGoogle Scholar

  • [8] Liu Q., Hilsenbeck S., Gazitt Y., Arsenic trioxideinduced apoptosis in myeloma cells: p53-dependent G1 or G2/M cell cycle arrest, activation of caspase-8 or caspase-9, and synergy with APO2/TRAIL, Blood, 2003, 101, 4078–4087 http://dx.doi.org/10.1182/blood-2002-10-3231CrossrefGoogle Scholar

  • [9] Shao Q.S., Ye Z.Y., Ling Z.Q., Ke J.J., Cell cycle arrest and apoptotic cell death in cultured human gastric carcinoma cells mediated by arsenic trioxide, World J. Gastroenterol., 2005, 11, 3451–3456 Google Scholar

  • [10] Ishitsuka K., Ikeda R., Utsunomiya A., Uozumi K., Hanada S., Suzuki S., et al., Arsenic trioxide induces apoptosis in HTLV-I infected T-cell lines and fresh adult T-cell leukemia cells through CD95 or tumor necrosis factor alpha receptor independent caspase activation, Leuk. Lymphoma, 2002, 43, 1107–1114 CrossrefGoogle Scholar

  • [11] Chow S.K., Chan J.Y., Fung K.P., Inhibition of cell proliferation and the action mechanisms of arsenic trioxide (As2O3) on human breast cancer cells, J. Cell Biochem., 2004, 93, 173–187 http://dx.doi.org/10.1002/jcb.20102CrossrefGoogle Scholar

  • [12] Kanzawa T., Zhang L., Xiao L., Germano I.M., Kondo Y., Kondo S., Arsenic trioxide induces autophagic cell death in malignant glioma cells by upregulation of mitochondrial cell death protein BNIP3, Oncogene, 2005, 24, 980–991 http://dx.doi.org/10.1038/sj.onc.1208095CrossrefGoogle Scholar

  • [13] Uslu R., Sanli U.A., Sezgin C., Karabulut B., Terzioglu E., Omay S.B., et al., Arsenic trioxidemediated cytotoxicity and apoptosis in prostate and ovarian carcinoma cell lines, Clin. Cancer Res., 2000, 6, 4957–4964 Google Scholar

  • [14] Bornstein J., Sagi S., Haj A., Harroch J., Fares F., Arsenic Trioxide inhibits the growth of human ovarian carcinoma cell line, Gynecol. Oncol., 2005, 99, 726–729 http://dx.doi.org/10.1016/j.ygyno.2005.07.125CrossrefGoogle Scholar

  • [15] Davison K., Mann K.K., Waxman S., Miller W.H. Jr, JNK activation is a mediator of arsenic trioxideinduced apoptosis in acute promyelocytic leukemia cells, Blood, 2004, 103, 3496–3502 http://dx.doi.org/10.1182/blood-2003-05-1412CrossrefGoogle Scholar

  • [16] Kitamura K., Minami Y., Yamamoto K., Akao Y., Kiyoi H., Saito H., et al., Involvement of CD95-independent caspase 8 activation in arsenic trioxide-induced apoptosis, Leukemia, 2000, 14, 1743–1750 http://dx.doi.org/10.1038/sj.leu.2401900CrossrefGoogle Scholar

  • [17] Mathas S., Lietz A., Janz M., Hinz M., Jundt F., Scheidereit C., et al., Inhibition of NF-kappaB essentially contributes to arsenic-induced apoptosis, Blood, 2003, 102, 1028–1034 http://dx.doi.org/10.1182/blood-2002-04-1154CrossrefGoogle Scholar

  • [18] Miller W.H. Jr, Schipper H.M., Lee J.S., Singer J., Waxman S., Mechanisms of action of arsenic trioxide, Cancer Res., 2002, 62, 3893–3903 Google Scholar

  • [19] Muscarella D.E., Bloom S.E., Differential activation of the c-Jun N-terminal kinase pathway in arseniteinduced apoptosis and sensitization of chemically resistant compared to susceptible B-lymphoma cell lines, Toxicol. Sci., 2002, 68, 82–92 http://dx.doi.org/10.1093/toxsci/68.1.82CrossrefGoogle Scholar

  • [20] Abercrombie M., The crawling movement of metazoan cells, Proc. R. Soc. Lond. B. Biol. Sci., 1980, 207, 129–147 http://dx.doi.org/10.1098/rspb.1980.0017CrossrefGoogle Scholar

  • [21] Carlier M.F., Ressad F., Pantaloni D., Control of actin dynamics in cell motility. Role of ADF/cofilin, J. Biol. Chem., 1999, 274, 33827–33830 http://dx.doi.org/10.1074/jbc.274.48.33827CrossrefGoogle Scholar

  • [22] Grzanka A., Dykiert P., Izdebska M., Grzanka D., The involvement of F-actin in apoptotic body formation in CHOAA8 cells treated with doxorubicin, Med. Biol. Sci., 2005, 19, 49–54 Google Scholar

  • [23] Rando O.J., Zhao K., Crabtree G.R., Searching for a function for nuclear actin, Trends Cell Biol., 2000, 10, 92–97 http://dx.doi.org/10.1016/S0962-8924(99)01713-4CrossrefGoogle Scholar

  • [24] Pederson T., As functional nuclear actin comes into view, is it globular, filamentous, or both?, J. Cell Biol., 2008, 17, 1061–1064 http://dx.doi.org/10.1083/jcb.200709082CrossrefGoogle Scholar

  • [25] Sauman I., Berry S.J., An actin infrastructure is associated with eukaryotic chromosomes: structural and functional significance, Eur. J. Cell Biol., 1994, 64, 348–356 Google Scholar

  • [26] Nishida E., Iida K., Yonezawa N., Koyasu S., Yahara I., Sakai H., Cofilin is a component of intranuclear and cytoplasmic actin rods induced in cultured cells, Proc. Natl. Acad. Sci. USA, 1987, 84, 5262–5266 http://dx.doi.org/10.1073/pnas.84.15.5262CrossrefGoogle Scholar

  • [27] Shestakova E.A., Motuz L.P., Minin A.A., Gavrilova L.P., Study of localization of the protein-synthesizing machinery along actin filament bundles, Cell Biol., Int., 1993, 17, 409–416 http://dx.doi.org/10.1006/cbir.1993.1079CrossrefGoogle Scholar

  • [28] Milankov K., De Boni U., Cytochemical localization of actin and myosin aggregates in interphase nuclei in situ, Exp. Cell Res., 1993, 209, 189–199 http://dx.doi.org/10.1006/excr.1993.1301CrossrefGoogle Scholar

  • [29] Soyer-Gobillard M.O., Ausseil J., Géraud M.L., Nuclear and cytoplasmic actin in dinoflagellates, Biol. Cell, 1996, 87, 17–35 http://dx.doi.org/10.1016/S0248-4900(97)89834-6CrossrefGoogle Scholar

  • [30] Funaki K., Katsumoto T., Iino A., Immunocytochemical localization of actin in the nucleolus of rat oocytes, Biol. Cell, 1995, 84, 139–146 http://dx.doi.org/10.1016/0248-4900(96)89423-8CrossrefGoogle Scholar

  • [31] Zhao K., Wang W., Rando O.J., Xue Y., Swiderek K., Kuo A., et al., Rapid and phosphoinositoldependent binding of the SWI/SNF-like BAF complex to chromatin after T lymphocyte receptor signaling, Cell, 1998, 95, 625–636 http://dx.doi.org/10.1016/S0092-8674(00)81633-5CrossrefGoogle Scholar

  • [32] Percipalle P., Zhao J., Pope B., Weeds A., Lindberg U., Daneholt B., Actin bound to the heterogeneous nuclear ribonucleoprotein hrp36 is associated with Balbiani ring mRNA from the gene to polysomes, J. Cell Biol., 2001, 153, 229–236 http://dx.doi.org/10.1083/jcb.153.1.229CrossrefGoogle Scholar

  • [33] Sahlas D.J., Milankov K., Park P.C., De Boni U., Distribution of snRNPs, splicing factor SC-35 and actin in interphase nuclei: immunocytochemical evidence for differential distribution during changes in functional states, J. Cell Sci., 1993, 105, 347–357 Google Scholar

  • [34] Hayashi T., Hideshima T., Akiyama M., Richardson P., Schlossman R.L., Chauhan D., et al., Arsenic trioxide inhibits growth of human multiple myeloma cells in the bone marrow microenvironment, Mol. Cancer Ther., 2002, 1, 851–860 Google Scholar

  • [35] Kerbauy D.M., Lesnikov V., Abbasi N., Seal S., Scott B., Deeg H.J., NF-kappaB and FLIP in arsenic trioxide (ATO)-induced apoptosis in myelodysplastic syndromes (MDSs), Blood, 2005, 106, 3917–3925 http://dx.doi.org/10.1182/blood-2005-04-1424CrossrefGoogle Scholar

  • [36] Zhang W., Ohnishi K., Shigeno K., Fujisawa S., Naito K., Nakamura S., et al., The induction of apoptosis and cell cycle arrest by arsenic trioxide in lymphoid neoplasms, Leukemia, 1998, 12, 1383–1391 http://dx.doi.org/10.1038/sj.leu.2401112CrossrefGoogle Scholar

  • [37] Shen Z.Y., Xu L.Y., Li E.M., Li J.T., Chen M.H., Shen J., et al., Ezrin, actin and cytoskeleton in apoptosis of esophageal epithelial cells induced by arsenic trioxide, Int. J. Mol. Med., 2003, 12, 341–347 Google Scholar

  • [38] Grzanka A., Grzanka D., Orlikowska M., Cytoskeletal reorganization during process of apoptosis induced by cytostatic drugs in K-562 and HL-60 leukemia cell lines, Biochem. Pharmacol., 2003, 66, 1611–1617 http://dx.doi.org/10.1016/S0006-2952(03)00532-XCrossrefGoogle Scholar

  • [39] Veselska R., Zitterbart K., Jelinkova S., Neradil J., Svoboda A., Specific cytoskeleton changes during apoptosis accompanying induced differentiation of HL-60 myeloid leukemia cells, Oncol. Rep., 2003, 10, 1049–1058 Google Scholar

  • [40] Olins A.L., Herrmann H., Lichter P., Olins D.E., Retinoic acid differentiation of HL-60 cells promotes cytoskeletal polarization, Exp. Cell Res., 2000, 254, 130–142 http://dx.doi.org/10.1006/excr.1999.4727CrossrefGoogle Scholar

  • [41] Grzanka A., Grzanka D., Orlikowska M., Fluorescence and ultrastructural localization of actin distribution patterns in the nucleus of HL-60 and K-562 cell lines treated with cytostatic drugs, Oncol. Rep., 2004, 11, 765–770 Google Scholar

  • [42] Pederson T., Aebi U., Actin in the nucleus: what form and what for?, J. Struct. Biol., 2002, 140, 3–9 http://dx.doi.org/10.1016/S1047-8477(02)00528-2CrossrefGoogle Scholar

  • [43] Pederson T., Aebi U., Nuclear actin extends, with no contraction in sight, Mol. Biol. Cell, 2005, 16, 5055–5060 http://dx.doi.org/10.1091/mbc.E05-07-0656CrossrefGoogle Scholar

  • [44] Olave I.A., Reck-Peterson S., Crabtree G.R., Nuclear actin and actin-related proteins in chromatin remodeling, Annu. Rev. Biochem., 2002, 71, 755–781 http://dx.doi.org/10.1146/annurev.biochem.71.110601.135507CrossrefGoogle Scholar

  • [45] Widlak P., Palyvoda O., Kumala S., Garrard W.T., Modeling apoptotic chromatin condensation in normal cell nuclei, J. Biol. Chem., 2002, 277, 21683–21690 http://dx.doi.org/10.1074/jbc.M201027200CrossrefGoogle Scholar

  • [46] McDonald D., Carrero G., Andrin C., de Vries G., Hendzel M.J., Nucleoplasmic beta-actin exists in a dynamic equilibrium between low-mobility polymeric species and rapidly diffusing populations, J. Cell Biol., 2006, 172, 541–552 http://dx.doi.org/10.1083/jcb.200507101CrossrefGoogle Scholar

  • [47] Starr D., Han M., Role of ANC-1 in tethering nuclei to the actin cytoskeleton, Science, 2002, 298, 406–409 http://dx.doi.org/10.1126/science.1075119CrossrefGoogle Scholar

  • [48] Hofmann W., Reichart B., Ewald A., Muller E., Schmitt I., Stauber R.H., et al., Cofactor requirements for nuclear export of Rev response element (RRE)- and constitutive transport element (CTE)-containing retroviral RNAs. An unexpected role for actin, J. Cell Biol., 2001, 152, 895–910 http://dx.doi.org/10.1083/jcb.152.5.895CrossrefGoogle Scholar

  • [49] Wasser M., Chia W., The EAST protein of drosophila controls an expandable nuclear endoskeleton, Nat. Cell Biol., 2000, 2, 268–275 http://dx.doi.org/10.1038/35010535CrossrefGoogle Scholar

  • [50] Park J.W., Choi Y.J., Jang M.A., Baek S.H., Lim J.H., Passaniti T., et al., Arsenic trioxide induces G2/M growth arrest and apoptosis after caspase-3 activation and bcl- phosphorylation in promonocytic U937 cells, Biochem. Biophys. Res. Commun., 2001, 286, 726–734 http://dx.doi.org/10.1006/bbrc.2001.5416Google Scholar

  • [51] Ishitsuka K., Hanada S., Uozumi K., Utsunomiya A., Arima T., Arsenic trioxide and the growth of human T-cell leukemia virus type I infected T-cell lines, Leuk. Lymphoma, 2000, 37, 649–655 CrossrefGoogle Scholar

About the article

Published Online: 2009-07-26

Published in Print: 2009-09-01

Citation Information: Open Life Sciences, Volume 4, Issue 3, Pages 351–361, ISSN (Online) 2391-5412, DOI: https://doi.org/10.2478/s11535-009-0021-5.

Export Citation

© 2009 Versita Warsaw. This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License. BY-NC-ND 3.0

Comments (0)

Please log in or register to comment.
Log in