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Article

Cotylenin A and tyrosine kinase inhibitors synergistically inhibit the growth of chronic myeloid leukemia cells

  • Authors:
    • Fumiyoshi Ikejiri
    • Yoshio Honma
    • Takahiro Okada
    • Takeshi Urano
    • Junji Suzumiya
  • View Affiliations / Copyright

    Affiliations: Department of Oncology/Hematology, Faculty of Medicine, Shimane University, Izumo, Shimane 6938501, Japan, Department of Biochemistry, Faculty of Medicine, Shimane University, Izumo, Shimane 6938501, Japan
  • Pages: 2061-2068
    |
    Published online on: April 2, 2018
       https://doi.org/10.3892/ijo.2018.4350
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Abstract

The treatment of chronic myeloid leukemia (CML) with tyrosine kinase inhibitors (TKIs) has substantially extended patient survival. However, TKIs do not effectively eliminate CML stem cells. In fact, CML stem cells persist and cause relapse in the majority of patients upon discontinuation of the drug treatment. Transcriptomic and proteomic analyses have revealed that p53 and c-Myc play defining roles in CML stem cell survival, suggesting that the dual targeting of p53 and c-Myc may selectively eliminate stem cells in patients with CML. Since the downregulation of c-Myc and then upregulation of p21 (a target gene of p53) are commonly observed during the differentiation of acute myeloid leukemia cells induced by differentiation inducers, we hypothesized that differentiation-inducing agents may be useful in regulating c-Myc and p53 expression in CML cells. In the present study, we demonstrate that some differentiation-inducing agents effectively suppress the self-renewal ability of CML cells, and that the combination of these inducers with TKIs results in significantly greater inhibitory effects on CML cell growth compared to the use of TKIs or the inducer alone. The KU812 cells were treated with various concentrations of the inducers in the presence or absence of 30 nM imatinib for 4 days. Among the differentiation inducers we tested, cotylenin A (CN-A) was the most potent at inhibiting the self-renewal ability of the CML cells. CN-A induced the robust expression of CD38, a marker of committed progenitor and more differentiated myelomonocytic cells, and rapidly suppressed c-Myc expression and upregulated p21 expression in CML cells. Thus, these results suggest that CN-A may have potential to promote the elimination of stem cells in CML.
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1 

Graham SM, Jørgensen HG, Allan E, Pearson C, Alcorn MJ, Richmond L and Holyoake TL: Primitive, quiescent, Philadelphia-positive stem cells from patients with chronic myeloid leukemia are insensitive to STI571 in vitro. Blood. 99:319–325. 2002. View Article : Google Scholar

2 

Mahon FX, Réa D, Guilhot J, Guilhot F, Huguet F, Nicolini F, Legros L, Charbonnier A, Guerci A, Varet B, et al Intergroupe Français des Leucémies Myéloïdes Chroniques: Discontinuation of imatinib in patients with chronic myeloid leukaemia who have maintained complete molecular remission for at least 2 years: The prospective, multicentre Stop Imatinib (STIM) trial. Lancet Oncol. 11:1029–1035. 2010. View Article : Google Scholar

3 

Corbin AS, Agarwal A, Loriaux M, Cortes J, Deininger MW and Druker BJ: Human chronic myeloid leukemia stem cells are insensitive to imatinib despite inhibition of BCR-ABL activity. J Clin Invest. 121:396–409. 2011. View Article : Google Scholar

4 

Abraham SA, Hopcroft LE, Carrick E, Drotar ME, Dunn K, Williamson AJ, Korfi K, Baquero P, Park LE, Scott MT, et al: Dual targeting of p53 and c-MYC selectively eliminates leukaemic stem cells. Nature. 534:341–346. 2016. View Article : Google Scholar

5 

Collins SJ, Bodner A, Ting R and Gallo RC: Induction of morphological and functional differentiation of human promyelocytic leukemia cells (HL-60) by componuds which induce differentiation of murine leukemia cells. Int J Cancer. 25:213–218. 1980. View Article : Google Scholar

6 

Honma Y: Cotylenin A - a plant growth regulator as a differentiation-inducing agent against myeloid leukemia. Leuk Lymphoma. 43:1169–1178. 2002. View Article : Google Scholar

7 

Ishii Y, Kasukabe T and Honma Y: Immediate up-regulation of the calcium-binding protein S100P and its involvement in the cytokinin-induced differentiation of human myeloid leukemia cells. Biochim Biophys Acta. 1745:156–165. 2005. View Article : Google Scholar

8 

Ishii Y, Kasukabe T and Honma Y: Induction of CCAAT/enhancer binding protein-delta by cytokinins, but not by retinoic acid, during granulocytic differentiation of human myeloid leukaemia cells. Br J Haematol. 128:540–547. 2005. View Article : Google Scholar

9 

Tsumura H, Akimoto M, Kiyota H, Ishii Y, Ishikura H and Honma Y: Gene expression profiles in differentiating leukemia cells induced by methyl jasmonate are similar to those of cytokinins and methyl jasmonate analogs induce the differentiation of human leukemia cells in primary culture. Leukemia. 23:753–760. 2009. View Article : Google Scholar

10 

Liebermann DA and Hoffman B: Differentiation primary response genes and proto-oncogenes as positive and negative regulators of terminal hematopoietic cell differentiation. Stem Cells. 12:352–369. 1994. View Article : Google Scholar

11 

Dimberg A, Bahram F, Karlberg I, Larsson LG, Nilsson K and Oberg F: Retinoic acid-induced cell cycle arrest of human myeloid cell lines is associated with sequential down-regulation of c-Myc and cyclin E and post-transcriptional up-regulation of p27(Kip1). Blood. 99:2199–2206. 2002. View Article : Google Scholar

12 

Hu XT and Zuckerman KS: Role of cell cycle regulatory molecules in retinoic acid- and vitamin D3-induced differentiation of acute myeloid leukaemia cells. Cell Prolif. 47:200–210. 2014. View Article : Google Scholar

13 

Yamada K, Honma Y, Asahi KI, Sassa T, Hino KI and Tomoyasu S: Differentiation of human acute myeloid leukaemia cells in primary culture in response to cotylenin A, a plant growth regulator. Br J Haematol. 114:814–821. 2001. View Article : Google Scholar

14 

Honma Y, Ishii Y, Sassa T and Asahi K: Treatment of human promyelocytic leukemia in the SCID mouse model with cotylenin A, an inducer of myelomonocytic differentiation of leukemia cells. Leuk Res. 27:1019–1025. 2003. View Article : Google Scholar

15 

Lozzio BB and Lozzio CB: Properties of the K562 cell line derived from a patient with chronic myeloid leukemia. Int J Cancer. 19:1361977. View Article : Google Scholar

16 

Kishi K: A new leukemia cell line with Philadelphia chromosome characterized as basophil precursors. Leuk Res. 9:381–390. 1985. View Article : Google Scholar

17 

Maniwa Y, Kasukabe T and Kumakura S: Vitamin K2 and cotylenin A synergistically induce monocytic differentiation and growth arrest along with the suppression of c-MYC expression and induction of cyclin G2 expression in human leukemia HL-60 cells. Int J Oncol. 47:473–480. 2015. View Article : Google Scholar

18 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−ΔΔC(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar

19 

Terstappen LW, Huang S, Safford M, Lansdorp PM and Loken MR: Sequential generations of hematopoietic colonies derived from single nonlineage-committed CD34+CD38− progenitor cells. Blood. 77:1218–1227. 1991.

20 

Wang Z, Liu Z, Wu X, Chu S, Wang J, Yuan H, Roth M, Yuan YC, Bhatia R and Chen W: ATRA-induced cellular differentiation and CD38 expression inhibits acquisition of BCR-ABL mutations for CML acquired resistance. PLoS Genet. 10:e10044142014. View Article : Google Scholar

21 

Takahashi T, Honma Y, Miyake T, Adachi K, Takami S, Okada M, Kumanomidou S, Ikejiri F, Jo Y, Onishi C, et al: Synergistic combination therapy with cotylenin A and vincristine in multiple myeloma models. Int J Oncol. 46:1801–1809. 2015. View Article : Google Scholar

22 

Kawakami K, Hattori M, Inoue T, Maruyama Y, Ohkanda J, Kato N, Tongu M, Yamada T, Akimoto M, Takenaga K, et al: A novel fusicoccin derivative preferentially targets hypoxic tumor cells and inhibits tumor growth in xenografts. Anticancer Agents Med Chem. 12:791–800. 2012. View Article : Google Scholar

23 

Miyake T, Honma Y, Urano T, Kato N and Suzumiya J: Combined treatment with tamoxifen and a fusicoccin derivative (ISIR-042) to overcome resistance to therapy and to enhance the antitumor activity of 5-fluorouracil and gemcitabine in pancreatic cancer cells. Int J Oncol. 47:315–324. 2015. View Article : Google Scholar

24 

Honma Y, Ishii Y, Yamamoto-Yamaguchi Y, Sassa T and Asahi K: Cotylenin A, a differentiation-inducing agent, and IFN-alpha cooperatively induce apoptosis and have an antitumor effect on human non-small cell lung carcinoma cells in nude mice. Cancer Res. 63:3659–3666. 2003.

25 

Oecking C, Eckerskorn C and Weiler EW: The fusicoccin receptor of plants is a member of the 14-3-3 superfamily of eukaryotic regulatory proteins. FEBS Lett. 352:163–166. 1994. View Article : Google Scholar

26 

Rittinger K, Budman J, Xu J, Volinia S, Cantley LC, Smerdon SJ, Gamblin SJ and Yaffe MB: Structural analysis of 14-3-3 phosphopeptide complexes identifies a dual role for the nuclear export signal of 14-3-3 in ligand binding. Mol Cell. 4:153–166. 1999. View Article : Google Scholar

27 

Fujita N, Sato S and Tsuruo T: Phosphorylation of p27Kip1 at threonine 198 by p90 ribosomal protein S6 kinases promotes its binding to 14-3-3 and cytoplasmic localization. J Biol Chem. 278:49254–49260. 2003. View Article : Google Scholar

28 

el-Deiry WS, Tokino T, Velculescu VE, Levy DB, Parsons R, Trent JM, Lin D, Mercer WE, Kinzler KW and Vogelstein B: WAF1, a potential mediator of p53 tumor suppression. Cell. 75:817–825. 1993. View Article : Google Scholar

29 

Moslehi JJ and Deininger M: Tyrosine kinase inhibitor-associated cardiovascular toxicity in chronic myeloid leukemia. J Clin Oncol. 33:4210–4218. 2015. View Article : Google Scholar

30 

Caldemeyer L, Dugan M, Edwards J and Akard L: Long-term side effects of tyrosine kinase inhibitors in chronic myeloid leukemia. Curr Hematol Malig Rep. 11:71–79. 2016. View Article : Google Scholar

31 

Ågerstam H, Hansen N, von Palffy S, Sandén C, Reckzeh K, Karlsson C, Lilljebjörn H, Landberg N, Askmyr M, Högberg C, et al: IL1RAP antibodies block IL-1-induced expansion of candidate CML stem cells and mediate cell killing in xenograft models. Blood. 128:2683–2693. 2016. View Article : Google Scholar

32 

Zhang B, Chu S, Agarwal P, Campbell VL, Hopcroft L, Jørgensen HG, Lin A, Gaal K, Holyoake TL and Bhatia R: Inhibition of interleukin-1 signaling enhances elimination of tyrosine kinase inhibitor-treated CML stem cells. Blood. 128:2671–2682. 2016. View Article : Google Scholar

33 

Cheloni G, Tanturli M, Tusa I, Ho DeSouza N, Shan Y, Gozzini A, Mazurier F, Rovida E, Li S and Dello Sbarba P: Targeting chronic myeloid leukemia stem cells with the hypoxia-inducible factor inhibitor acriflavine. Blood. 130:655–665. 2017. View Article : Google Scholar

34 

Kuntz EM, Baquero P, Michie AM, Dunn K, Tardito S, Holyoake TL, Helgason GV and Gottlieb E: Targeting mitochondrial oxidative phosphorylation eradicates therapy-resistant chronic myeloid leukemia stem cells. Nat Med. 23:1234–1240. 2017. View Article : Google Scholar

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Copy and paste a formatted citation
Spandidos Publications style
Ikejiri F, Honma Y, Okada T, Urano T and Suzumiya J: Cotylenin A and tyrosine kinase inhibitors synergistically inhibit the growth of chronic myeloid leukemia cells. Int J Oncol 52: 2061-2068, 2018.
APA
Ikejiri, F., Honma, Y., Okada, T., Urano, T., & Suzumiya, J. (2018). Cotylenin A and tyrosine kinase inhibitors synergistically inhibit the growth of chronic myeloid leukemia cells. International Journal of Oncology, 52, 2061-2068. https://doi.org/10.3892/ijo.2018.4350
MLA
Ikejiri, F., Honma, Y., Okada, T., Urano, T., Suzumiya, J."Cotylenin A and tyrosine kinase inhibitors synergistically inhibit the growth of chronic myeloid leukemia cells". International Journal of Oncology 52.6 (2018): 2061-2068.
Chicago
Ikejiri, F., Honma, Y., Okada, T., Urano, T., Suzumiya, J."Cotylenin A and tyrosine kinase inhibitors synergistically inhibit the growth of chronic myeloid leukemia cells". International Journal of Oncology 52, no. 6 (2018): 2061-2068. https://doi.org/10.3892/ijo.2018.4350
Copy and paste a formatted citation
x
Spandidos Publications style
Ikejiri F, Honma Y, Okada T, Urano T and Suzumiya J: Cotylenin A and tyrosine kinase inhibitors synergistically inhibit the growth of chronic myeloid leukemia cells. Int J Oncol 52: 2061-2068, 2018.
APA
Ikejiri, F., Honma, Y., Okada, T., Urano, T., & Suzumiya, J. (2018). Cotylenin A and tyrosine kinase inhibitors synergistically inhibit the growth of chronic myeloid leukemia cells. International Journal of Oncology, 52, 2061-2068. https://doi.org/10.3892/ijo.2018.4350
MLA
Ikejiri, F., Honma, Y., Okada, T., Urano, T., Suzumiya, J."Cotylenin A and tyrosine kinase inhibitors synergistically inhibit the growth of chronic myeloid leukemia cells". International Journal of Oncology 52.6 (2018): 2061-2068.
Chicago
Ikejiri, F., Honma, Y., Okada, T., Urano, T., Suzumiya, J."Cotylenin A and tyrosine kinase inhibitors synergistically inhibit the growth of chronic myeloid leukemia cells". International Journal of Oncology 52, no. 6 (2018): 2061-2068. https://doi.org/10.3892/ijo.2018.4350
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