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Clofarabine‑phytochemical combination exposures in CML cells inhibit DNA methylation machinery, upregulate tumor suppressor genes and promote caspase‑dependent apoptosis

  • Authors:
    • Agnieszka Kaufman‑Szymczyk
    • Katarzyna Majda
    • Agata Szuławska‑Mroczek
    • Krystyna Fabianowska‑Majewska
    • Katarzyna Lubecka
  • View Affiliations / Copyright

    Affiliations: Department of Biomedical Chemistry, Faculty of Health Sciences, Medical University of Lodz, 92‑215 Lodz, Poland, Faculty of Medicine, Lazarski University, 02‑662 Warsaw, Poland
    Copyright: © Kaufman‑Szymczyk et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 3597-3608
    |
    Published online on: August 27, 2019
       https://doi.org/10.3892/mmr.2019.10619
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Abstract

Clofarabine (2‑chloro‑2'‑fluoro‑2'‑deoxyarabinosyladenine, CIF), a second‑generation 2'‑deoxyadenosine analog, possesses a variety of anti‑cancer activities, including the capacity to modulate DNA methylation marks. Bioactive nutrients, including resveratrol (RSV) and all‑trans retinoic acid (ATRA) have been indicated to regulate epigenetic machinery in malignant cells. The purpose of the current study was to evaluate whether the tested phytochemicals, RSV or ATRA, can improve the therapeutic epigenetic effects of CIF in chronic myeloid leukemia (CML) cells. The present study investigates, to the best of our knowledge, for the first time, the influence of CIF in combination with RSV or ATRA on the expression of relevant modifiers of DNA methylation machinery, including DNA Methyltransferase 1 (DNMT1) and Cyclin dependent kinase inhibitor 1A (CDKN1A) in CML cells. Subsequently, the combinatorial effects on promoter methylation and transcript levels of methylation‑silenced tumor suppressor genes (TSGs), including phosphatase and tensin homologue (PTEN) and retinoic acid receptor beta (RARB), were estimated using MSRA and qPCR, respectively. The tested TSGs were chosen according to bioinformatical analysis of publicly available clinical data of human DNA methylation and gene expression arrays in leukemia patients. The K562 cell line was used as an experimental CML in vitro model. Following a period of 72 h exposure of K562 cells, the tested combinations led to significant cell growth inhibition and induction of caspase‑3‑dependent apoptosis. These observations were accompanied by DNMT1 downregulation and CDKN1A upregulation, with a concomitant enhanced decrease in DNMT1 protein level, especially after ATRA treatment with CIF. Concurrent methylation‑mediated RARB and PTEN reactivation was detected. The results of the current study demonstrated that CIF that was used in combination with the tested phytochemicals, RSV or ATRA, exhibited a greater ability to remodel DNA methylation marks and promote cell death in CML cells. These results may support the application of CIF combinations with natural bioactive agents in anti‑leukemic epigenetic therapy.
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View References

1 

Chen Y, Peng C, Li D and Li S: Molecular and cellular bases of chronic myeloid leukemia. Protein Cell. 1:124–132. 2010. View Article : Google Scholar : PubMed/NCBI

2 

Soverini S, de Benedittis C, Mancini M and Martinelli G: Mutations in the BCR-ABL1 kinase domain and elsewhere in chronic myeloid leukemia. Clin Lymphoma Myeloma Leuk. 15 (Suppl):S120–S128. 2015. View Article : Google Scholar : PubMed/NCBI

3 

Druker BJ, Talpaz M, Resta DJ, Peng B, Buchdunger E, Ford JM, Lydon NB, Kantarjian H, Capdeville R, Ohno-Jones S and Sawyers CL: Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med. 344:1031–1037. 2001. View Article : Google Scholar : PubMed/NCBI

4 

Bhatia R, Holtz M, Niu N, Gray R, Snyder DS, Sawyers CL, Arber DA, Slovak ML and Forman SJ: Persistence of malignant hematopoietic progenitors in chronic myelogenous leukemia patients in complete cytogenetic remission following imatinib mesylate treatment. Blood. 101:4701–4707. 2003. View Article : Google Scholar : PubMed/NCBI

5 

Chomel JC, Bonnet ML, Sorel N, Bertrand A, Meunier MC, Fichelson S, Melkus M, Bennaceur-Griscelli A, Guilhot F and Turhan AG: Leukemic stem cell persistence in chronic myeloid leukemia patients with sustained undetectable molecular residual disease. Blood. 118:3657–3660. 2011. View Article : Google Scholar : PubMed/NCBI

6 

Leo E and Martinelli G: DNA methylation in chronic myeloid leukemia. J Mol Genet Med. 8:1182014.

7 

Koschmieder S and Vetrie D: Epigenetic dysregulation in chronic myeloid leukaemia: A myriad of mechanisms and therapeutic options. Semin Cancer Biol. 51:180–197. 2018. View Article : Google Scholar : PubMed/NCBI

8 

Robertson KD: Epigenetic mechanisms of gene regulationDNA Methylation and Cancer Therapy. Medical Intelligence Unit. Springer; Boston, MA: pp. 13–30. 2005, View Article : Google Scholar

9 

Jaenisch R and Bird A: Epigenetic regulation of gene expression: How the genome integrates intrinsic and environmental signals. Nat Genet. 33 (Suppl):S245–S254. 2003. View Article : Google Scholar

10 

Jones PA and Baylin SB: The epigenomics of cancer. Cell. 128:683–692. 2007. View Article : Google Scholar : PubMed/NCBI

11 

Chik F, Szyf M and Rabbani SA: Role of epigenetics in cancer initiation and progression. Adv Exp Med Biol. 720:91–104. 2011. View Article : Google Scholar : PubMed/NCBI

12 

Chen T and Li E: Structure and function of eukaryotic DNA methyltransferases. Curr Top Dev Biol. 60:55–89. 2004. View Article : Google Scholar : PubMed/NCBI

13 

Majda K, Kaufman-Szymczyk A, Lubecka-Pietruszewska K, Bednarek A and Fabianowska-Majewska K: Influence of clofarabine on transcriptional activity of PTEN, APC, RARB2, ZAP70 genes in K562 cells. Anticancer Res. 30:4601–4606. 2010.PubMed/NCBI

14 

Lubecka-Pietruszewska K, Kaufman-Szymczyk A, Stefanska B, Cebula-Obrzut B, Smolewski P and Fabianowska-Majewska K: Clofarabine, a novel adenosine analogue, reactivates DNA methylation-silenced tumour suppressor genes and inhibits cell growth in breast cancer cells. Eur J Pharmacol. 723:276–287. 2014. View Article : Google Scholar : PubMed/NCBI

15 

Ghanem H Jabbour E, Faderl S, Ghandhi V, Plunkett W and Kantarjian H: Clofarabine in leukemia. Expert Rev Hematol. 3:15–22. 2010. View Article : Google Scholar : PubMed/NCBI

16 

Ghanem H, Kantarjian H, Ohanian M and Jabbour E: The role of clofarabine in acute myeloid leukemia. Leuk Lymphoma. 54:688–698. 2013. View Article : Google Scholar : PubMed/NCBI

17 

Stefanska B, Karlic H, Varga F, Fabianowska-Majewska K and Haslberger A: Epigenetic mechanisms in anti-cancer actions of bioactive food components-the implications in cancer prevention. Br J Pharmacol. 167:279–297. 2012. View Article : Google Scholar : PubMed/NCBI

18 

Stefanska B, Salamé P, Bednarek A and Fabianowska-Majewska K: Comparative effects of retinoic acid, vitamin D and resveratrol alone and in combination with adenosine analogues on methylation and expression of phosphatase and tensin homologue tumour suppressor gene in breast cancer cells. Br J Nutr. 107:781–790. 2012. View Article : Google Scholar : PubMed/NCBI

19 

Lubecka K, Kurzava L, Flower K, Buvala H, Zhang H, Teegarden D, Camarillo I, Suderman M, Kuang S, Andrisani O, et al: Stilbenoids remodel the DNA methylation patterns in breast cancer cells and inhibit oncogenic NOTCH signaling through epigenetic regulation of MAML2 transcriptional activity. Carcinogenesis. 37:656–668. 2016. View Article : Google Scholar : PubMed/NCBI

20 

Lee YJ, Lee YJ, Im JH, Won SY, Kim YB, Cho MK, Nam HS, Choi YJ and Lee SH: Synergistic anti-cancer effects of resveratrol and chemotherapeutic agent clofarabine against human malignant mesothelioma MSTO-211H cells. Food Chem Toxicol. 52:61–68. 2013. View Article : Google Scholar : PubMed/NCBI

21 

Lee YJ, Hwang IS, Lee YJ, Lee CH, Kim SH, Nam HS, Choi YJ and Lee SH: Knockdown of Bcl-xL enhances growth-inhibiting and apoptosis-inducing effects of resveratrol and clofarabine in malignant mesothelioma H-2452 cells. J Korean Med Sci. 29:1464–1472. 2014. View Article : Google Scholar : PubMed/NCBI

22 

Lee YJ, Lee YJ and Lee SH: Resveratrol and clofarabine induces a preferential apoptosis-activating effect on malignant mesothelioma cells by Mcl-1 down-regulation and caspase-3 activation. BMB Rep. 48:166–171. 2015. View Article : Google Scholar : PubMed/NCBI

23 

Kulkarni SS and Cantó C: The molecular targets of resveratrol. Biochim Biophys Acta. 1852:1114–1123. 2015. View Article : Google Scholar : PubMed/NCBI

24 

Theodosiou M, Laudet V and Schubert M: From carrot to clinic: An overview of the retinoic acid signaling pathway. Cell Mol Life Sci. 67:1423–1445. 2010. View Article : Google Scholar : PubMed/NCBI

25 

Tang XH and Gudas LJ: Retinoids, retinoic acid receptors, and cancer. Annu Rev Pathol. 6:345–364. 2011. View Article : Google Scholar : PubMed/NCBI

26 

Connolly R, Nguyen NK and Sukumar S: Molecular pathways: Current role and future directions of the retinoic acid pathway in cancer prevention and treatment. Clin Cancer Res. 19:1651–1659. 2013. View Article : Google Scholar : PubMed/NCBI

27 

Schenk T, Stengel S and Zelent A: Unlocking the potential of retinoic acid in anticancer therapy. Br J Cancer. 111:2039–2045. 2014. View Article : Google Scholar : PubMed/NCBI

28 

Zhang W and Xu J: DNA methyltransferases and their roles in tumorigenesis. Biomark Res. 5:12017. View Article : Google Scholar : PubMed/NCBI

29 

Wu Q, Chen ZM and Su WJ: Anticancer effect of retinoic acid via AP-1 activity repression is mediated by retinoic acid receptor alpha and beta in gastric cancer cells. Int J Biochem Cell Biol. 34:1102–1114. 2002. View Article : Google Scholar : PubMed/NCBI

30 

Stefanska B, Rudnicka K, Bednarek A and Fabianowska-Majewska K: Hypomethylation and induction of retinoic acid receptor beta 2 by concurrent action of adenosine analogues and natural compounds in breast cancer cells. Eur J Pharmacol. 638:47–53. 2010. View Article : Google Scholar : PubMed/NCBI

31 

McCabe MT, Davis JN and Day ML: Regulation of DNA methyltransferase 1 by the pRb/E2F1 pathway. Cancer Res. 65:3624–3632. 2005. View Article : Google Scholar : PubMed/NCBI

32 

Delavaine L and La Thangue NB: Control of E2F activity by p21Waf1/Cip1. Oncogene. 18:5381–5392. 1999. View Article : Google Scholar : PubMed/NCBI

33 

Chuang LS, Ian HI, Koh TW, Ng HH, Xu G and Li BF: Human DNA-(cytosine-5) methyltransferase-PCNA complex as a target for p21WAF1. Science. 277:1996–2000. 1997. View Article : Google Scholar : PubMed/NCBI

34 

Iida T, Suetake I, Tajima S, Morioka H, Ohta S, Obuse C and Tsurimoto T: PCNA clamp facilitates action of DNA cytosine methyltransferase 1 on hemimethylated DNA. Genes Cells. 7:997–1007. 2002. View Article : Google Scholar : PubMed/NCBI

35 

Yamada KM and Araki M: Tumor suppressor PTEN: Modulator of cell signaling, growth, migration and apoptosis. J Cell Sci. 114:2375–2382. 2001.PubMed/NCBI

36 

Iwase H, Omoto Y, Iwata H, Toyama T, Hara Y, Ando Y, Ito Y, Fujii Y and Kobayashi S: DNA methylation analysis at distal and proximal promoter regions of the oestrogen receptor gene in breast cancers. Br J Cancer. 80:1982–1986. 1999. View Article : Google Scholar : PubMed/NCBI

37 

Pfaffl MW, Horgan GW and Dempfle L: Relative expression software tool (REST) for group-wise comparison and statistical analysis of relative expression results in real-time PCR. Nucleic Acids Res. 30:e362002. View Article : Google Scholar : PubMed/NCBI

38 

Sui T, Ma L, Bai X, Li Q and Xu X: Resveratrol inhibits the phosphatidylinositide 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway in the human chronic myeloid leukemia K562 cell line. Oncol Lett. 7:2093–2098. 2014. View Article : Google Scholar : PubMed/NCBI

39 

Wang B, Liu J and Gong Z: Resveratrol induces apoptosis in K562 cells via the regulation of mitochondrial signaling pathways. Int J Clin Exp Med. 8:16926–16933. 2015.PubMed/NCBI

40 

Mizuno S, Chijiwa T, Okamura T, Akashi K, Fukumaki Y, Niho Y and Sasaki H: Expression of DNA methyltransferases DNMT1, 3A, and 3B in normal hematopoiesis and in acute and chronic myelogenous leukemia. Blood. 97:1172–1179. 2001. View Article : Google Scholar : PubMed/NCBI

41 

Tan HH and Porter AG: p21(WAF1) negatively regulates DNMT1 expression in mammalian cells. Biochem Biophys Res Commun. 382:171–176. 2009. View Article : Google Scholar : PubMed/NCBI

42 

Liu M, Iavarone A and Freedman LP: Transcriptional activation of the human p21(WAF1/CIP1) gene by retinoic acid receptor. Correlation with retinoid induction of U937 cell differentiation. J Biol Chem. 271:31723–31728. 1996. View Article : Google Scholar : PubMed/NCBI

43 

Yu Z, Li W, Lu Q, Wang L, Zhang X, Han P, Chen P and Pei Y: p21 is required for atRA-mediated growth inhibition of MEPM cells, which involves RAR. J Cell Biochem. 104:2185–2192. 2008. View Article : Google Scholar : PubMed/NCBI

44 

Bowers JL, Tyulmenkov VV, Jernigan SC and Klinge CM: Resveratrol acts as a mixed agonist/antagonist for estrogen receptors alpha and beta. Endocrinology. 141:3657–3667. 2000. View Article : Google Scholar : PubMed/NCBI

45 

Parveen A, Akash MS, Rehman K and Kyunn WW: Dual role of p21 in the progression of cancer and its treatment. Crit Rev Eukaryot Gene Expr. 26:49–62. 2016. View Article : Google Scholar : PubMed/NCBI

46 

Montiel-Duarte C, Cordeu L, Agirre X, Román-Gómez J, Jiménez-Velasco A, José-Eneriz ES, Gárate L, Andreu EJ, Calasanz MJ, Heiniger A, et al: Resistance to Imatinib mesylate-induced apoptosis in acute lymphoblastic leukemia is associated with PTEN down-regulation due to promoter hypermethylation. Leuk Res. 32:709–716. 2008. View Article : Google Scholar : PubMed/NCBI

47 

García JM, Silva J, Peña C, Garcia V, Rodríguez R, Cruz MA, Cantos B, Provencio M, España P and Bonilla F: Promoter methylation of the PTEN gene is a common molecular change in breast cancer. Genes Chromosomes Cancer. 41:117–124. 2004. View Article : Google Scholar : PubMed/NCBI

48 

Goel A, Arnold CN, Niedzwiecki D, Carethers JM, Dowell JM, Wasserman L, Compton C, Mayer RJ, Bertagnolli MM and Boland CR: Frequent inactivation of PTEN by promoter hypermethylation in microsatellite instability-high sporadic colorectal cancers. Cancer Res. 64:3014–3021. 2004. View Article : Google Scholar : PubMed/NCBI

49 

Wyczechowska D and Fabianowska-Majewska K: The effects of cladribine and fludarabine on DNA methylation in K562 cells. Biochem. Pharmacol. 65:219–225. 2003.

50 

Lefebvre B, Brand C, Flajollet S and Lefebvre P: Down-regulation of the tumour suppressor gene retinoic acid receptor beta2 through the phosphoinositide 3-knase/Akt signaling pathway. Mol Endocrinol. 20:2109–2121. 2006. View Article : Google Scholar : PubMed/NCBI

51 

Lussana F, Intermesoli T, Stefanoni P and Rambaldi A: Mechanisms of resistance to targeted therapies in chronic myeloid leukemia. Handb Exp Pharmacol. 249:231–250. 2018. View Article : Google Scholar : PubMed/NCBI

52 

Nishioka C, Ikezoe T, Yang J and Yokoyama A: Long-term exposure of leukemia cells to multi-targeted tyrosine kinase inhibitor induces activations of AKT, ERK and STAT5 signaling via epigenetic silencing of the PTEN gene. Leukemia. 24:1631–1640. 2010. View Article : Google Scholar : PubMed/NCBI

53 

Nishioka C, Ikezoe T, Yang J, Udaka K and Yokoyama A: Imatinib causes epigenetic alterations of PTEN gene via upregulation of DNA methyltransferases and polycomb group proteins. Blood Cancer J. 1:e482011. View Article : Google Scholar : PubMed/NCBI

54 

Can G, Cakir Z, Kartal M, Gunduz U and Baran Y: Apoptotic effects of resveratrol, a grape polyphenol, on imatinib-sensitive and resistant K562 chronic myeloid leukemia cells. Anticancer Res. 32:2673–2678. 2012.PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Kaufman‑Szymczyk A, Majda K, Szuławska‑Mroczek A, Fabianowska‑Majewska K and Lubecka K: Clofarabine‑phytochemical combination exposures in CML cells inhibit DNA methylation machinery, upregulate tumor suppressor genes and promote caspase‑dependent apoptosis. Mol Med Rep 20: 3597-3608, 2019.
APA
Kaufman‑Szymczyk, A., Majda, K., Szuławska‑Mroczek, A., Fabianowska‑Majewska, K., & Lubecka, K. (2019). Clofarabine‑phytochemical combination exposures in CML cells inhibit DNA methylation machinery, upregulate tumor suppressor genes and promote caspase‑dependent apoptosis. Molecular Medicine Reports, 20, 3597-3608. https://doi.org/10.3892/mmr.2019.10619
MLA
Kaufman‑Szymczyk, A., Majda, K., Szuławska‑Mroczek, A., Fabianowska‑Majewska, K., Lubecka, K."Clofarabine‑phytochemical combination exposures in CML cells inhibit DNA methylation machinery, upregulate tumor suppressor genes and promote caspase‑dependent apoptosis". Molecular Medicine Reports 20.4 (2019): 3597-3608.
Chicago
Kaufman‑Szymczyk, A., Majda, K., Szuławska‑Mroczek, A., Fabianowska‑Majewska, K., Lubecka, K."Clofarabine‑phytochemical combination exposures in CML cells inhibit DNA methylation machinery, upregulate tumor suppressor genes and promote caspase‑dependent apoptosis". Molecular Medicine Reports 20, no. 4 (2019): 3597-3608. https://doi.org/10.3892/mmr.2019.10619
Copy and paste a formatted citation
x
Spandidos Publications style
Kaufman‑Szymczyk A, Majda K, Szuławska‑Mroczek A, Fabianowska‑Majewska K and Lubecka K: Clofarabine‑phytochemical combination exposures in CML cells inhibit DNA methylation machinery, upregulate tumor suppressor genes and promote caspase‑dependent apoptosis. Mol Med Rep 20: 3597-3608, 2019.
APA
Kaufman‑Szymczyk, A., Majda, K., Szuławska‑Mroczek, A., Fabianowska‑Majewska, K., & Lubecka, K. (2019). Clofarabine‑phytochemical combination exposures in CML cells inhibit DNA methylation machinery, upregulate tumor suppressor genes and promote caspase‑dependent apoptosis. Molecular Medicine Reports, 20, 3597-3608. https://doi.org/10.3892/mmr.2019.10619
MLA
Kaufman‑Szymczyk, A., Majda, K., Szuławska‑Mroczek, A., Fabianowska‑Majewska, K., Lubecka, K."Clofarabine‑phytochemical combination exposures in CML cells inhibit DNA methylation machinery, upregulate tumor suppressor genes and promote caspase‑dependent apoptosis". Molecular Medicine Reports 20.4 (2019): 3597-3608.
Chicago
Kaufman‑Szymczyk, A., Majda, K., Szuławska‑Mroczek, A., Fabianowska‑Majewska, K., Lubecka, K."Clofarabine‑phytochemical combination exposures in CML cells inhibit DNA methylation machinery, upregulate tumor suppressor genes and promote caspase‑dependent apoptosis". Molecular Medicine Reports 20, no. 4 (2019): 3597-3608. https://doi.org/10.3892/mmr.2019.10619
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