Arsenic trioxide induction autophagy in human acute promyelocytic leukemia

authors:

avatar Faride shakerimoghadam , avatar Maedeh Dejamfekr , avatar Seyed Hamidollah Ghaffari , avatar Shahin Ahmadian , avatar Ali khaleghian ORCID , *

Koomesh: Vol.20, issue 4; 764-771
published online: March 25, 2018
article type: Research Article
received: November 01, 2017
accepted: February 01, 2018

how to cite: shakerimoghadam F, Dejamfekr M, Ghaffari S H, Ahmadian S, khaleghian A. Arsenic trioxide induction autophagy in human acute promyelocytic leukemia. koomesh. 2018;20(4):e153024. 

Abstract

  Introduction: Autophagy is a survival pathway required for cellular viability during starvation through catabolic self digestion of damaged proteins and organelles however, autophagy may result in cell death if it proceeds to completion. Although the exact mechanism of this process is not clear, it seems that proper regulation of autophagy can potentially contribute to the therapeutics of cancers. The aim of this study was to determine the role of Arsenic trioxide (As2O3) in the induction of autophagy in human acute promyelocytic leukemia. Materials and Methods: In this study, the role of autophagy in the As2O3-induced death of NB4 cells was assessed using electron microscopy. Also, quantitative real-time PCR method was used for expression of autophagy related genes in dose and Time dependent manner. Results: Our results showed that autophagy induces death in NB4 cells treated with arsenic trioxide. It was also found that the Atg7, Bclin1 and LC3 genes, which are essential genes for induction of autophagy, are the target of arsenic trioxide invasion. Conclusion: This study showed As2O3-induced autophagy plays an important role in eliminating leukemia cells and treatment of cancer.  

References

  • 1.

    Mizushima N, Levine B, Cuervo AM, Klionsky DJ. Autophagy fights disease through cellular self-digestion. Nature 2008; 451: 1069-1075.

  • 2.

    Klionsky DJ. Autophagy: from phenomenology to molecular understanding in less than a decade. Nat Rev Mol Cell Biol 2007; 8: 931-937.

  • 3.

    Nakatogawa H, Suzuki K, Kamada Y, Ohsumi Y. Dynamics and diversity in autophagy mechanisms: lessons from yeast. Nat Rev Mol Cell Biol 2009; 10: 458-467.

  • 4.

    Levine B, Kroemer G. Autophagy in the pathogenesis of disease. Cell 2008; 132: 27-42.

  • 5.

    Mizushima N. Autophagy: process and function. Genes Dev 2007; 21: 2861-2873.

  • 6.

    Mizushima N, Klionsky DJ. Protein turnover via autophagy: implications for metabolism. Annu Rev Nutr 2007; 27: 19-40.

  • 7.

    Pankiv S, Clausen TH, Lamark T, Brech A, Bruun JA, Outzen H, vervatn A, Bjrky G, Johansen T. p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy. J Biol Chem 2007; 282: 24131-24145.

  • 8.

    Pattingre S, Tassa A, Qu X, Garuti R, Liang XH, Mizushima N, et al. Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy. Cell 2005; 122: 927-939.

  • 9.

    A-niapour N, shokri gara geshlagi S, amani M, sharifi pasandi M, salehi H, niapour A. Effects of all trans retinoic acid on apoptosis induction and notch1, hes1 genes expression in gastric cancer cell line MKN-45. Koomesh 2016; 17: 1024-1032. (Persian).

  • 10.

    B- Jaafarinejad H, Ghanizadeh N, Ghahremanfard F, Barati M, Manouchehri Doulabi E, Kokhaei P. Effect of Beberine on the survivin gene expression in peripheral blood mononuclear cell of chronic lymphocytic leukemia patients in vitro. Koomesh 2017; 19: 227-232. (Persian).

  • 11.

    Wang ZY, Chen Z. Acute promyelocytic leukemia: from highly fatal to highly curable. Blood 2008; 111: 2505-2515.

  • 12.

    Sell S. Leukemia: stem cells, maturation arrest, and differentiation therapy. Stem Cell Rev 2005; 1: 197-205.

  • 13.

    Canestraro M, Galimberti S, Savli H, Palumbo GA, Tibullo D, Nagy B, et al. Synergistic antiproliferative effect of arsenic trioxide combined with bortezomib in HL60 cell line and primary blasts from patients affected by myeloproliferative disorders. Cancer Genet Cytogenet 2010; 199: 110-120.

  • 14.

    Westervelt P, Brown RA, Adkins DR, Khoury H, Curtin P, Hurd D, et al. Sudden death among patients with acute promyelocytic leukemia treated with arsenic trioxide. Blood 2001; 98: 266-271.

  • 15.

    Khaleghian A, Ghaffari SH, Ahmadian S, Alimoghaddam K, Ghavamzadeh A. Metabolism of arsenic trioxide in acute promyelocytic leukemia cells. J Cell Biochem 2014; 115: 1729-1739.

  • 16.

    Qu X, Zou Z, Sun Q, Luby-Phelps K, Cheng P, Hogan RN, et al. Autophagy gene-dependent clearance of apoptotic cells during embryonic development. Cell 2007; 128: 931-946.

  • 17.

    Russell RC, Yuan HX, Guan KL. Autophagy regulation by nutrient signaling. Cell Res 2014; 24: 42-57.

  • 18.

    Maiuri MC, Zalckvar E, Kimchi A, Kroemer G. Self-eating and self-killing: crosstalk between autophagy and apoptosis. Nat Rev Mol Cell Biol 2007; 8: 741-752.

  • 19.

    Miller WH, Schipper HM, Lee JS, Singer J, Waxman S. Mechanisms of action of arsenic trioxide. Cancer Res 2002; 62: 3893-3903.

  • 20.

    Isakson P, Bjrs M, Be SO, Simonsen A. Autophagy contributes to therapy-induced degradation of the PML/RARA oncoprotein. Blood 2010; 116: 2324-2331.

  • 21.

    Jun Z, Valerie L, Hugues T. Pathways of retinoicacidor arsenic trioxide. induced PML/RARa catabolism, role of oncogene degradation in disease remission. Oncogene 2001; 20: 7257-7265.

  • 22.

    Yoshida H, Kitamura K, Tanaka K, Omura S, Miyazaki T, Hachiya T, et al. Accelerated degradation of PML-retinoic acid receptor (PML-RARA) oncoprotein by all-trans-retinoic acid in acute promyelocytic leukemia: possible role of the proteasome pathway. Cancer Res 1996; 56: 2945-2948.

  • 23.

    Lallemand-Breitenbach V, Jeanne M, Benhenda S, Nasr R, Lei M, Peres L, et al. Arsenic degrades PML or PMLRAR through a SUMO-triggered RNF4/ubiquitin-mediated pathway. Nat Cell Biol 2008; 10: 547-555.

  • 24.

    Hu J, Liu YF, Wu CF, Xu F, Shen ZX, Zhu YM, et al. Long-term efficacy and safety of all-trans retinoic acid/arsenic trioxide-based therapy in newly diagnosed acute promyelocytic leukemia. Proc Natl Acad Sci U S A 2009; 106: 3342-3347.

  • 25.

    Bence NF, Sampat RM, Kopito RR. Impairment of the ubiquitin-proteasome system by protein aggregation. Science 2001; 292: 1552-1555.

  • 26.

    Liang XH, Jackson S, Seaman M, Brown K, Kempkes B, Hibshoosh H, Levine B. Induction of autophagy and inhibition of tumorigenesis by beclin 1. Nature 1999; 402: 672-676.

  • 27.

    Kamitsuji Y, Kuroda J, Kimura S, Toyokuni S, Watanabe K, Ashihara E, et al. The Bcr-Abl kinase inhibitor INNO-406 induces autophagy and different modes of cell death execution in Bcr-Abl-positive leukemias. Cell Death Differ 2008; 15: 1712-1722.

  • 28.

    Ertmer A, Huber V, Gilch S, Yoshimori T, Erfle V, Duyster J, et al. The anticancer drug imatinib induces cellular autophagy. Leukemia 2007; 21: 936-942.

  • 29.

    Goussetis DJ, Altman JK, Glaser H, McNeer JL, Tallman MS, Platanias LC. Autophagy is a critical mechanism for the induction of the antileukemic effects of arsenic trioxide. J Biol Chem 2010; 285: 29989-29997.

  • 30.

    Mario G, Salvador-Montoliu N, Fueyo A, Knecht E, Mizushima N, Lpez-Otn C. Tissue-specific autophagy alterations and increased tumorigenesis in mice deficient in Atg4C/autophagin-3. J Biol Chem 2007; 282: 18573-18583.

  • 31.

    Ren Y, Xie Y, Chai L, Wang S, Cheng M. Autophagy modification augmented the treatment effects initiated by arsenic trioxide in NB4 cells. Med Oncol 2011; 28: 231-236.

  • 32.

    Apel A, Zentgraf H, Bchler MW, Herr I. AutophagyA doubleedged sword in oncology. Int J Cancer 2009; 125: 991-995.

  • 33.

    Yu L, Lenardo MJ, Baehrecke EH. Autophagy and caspases: a new cell death program. Cell Cycle 2004; 3: 1122-1124.

  • 34.

    Eisenberg-Lerner A, Kimchi A. The paradox of autophagy and its implication in cancer etiology and therapy. Apoptosis 2009; 14: 376-391.

  • 35.

    Platanias LC. Biological responses to arsenic compounds. J Biol Chem 2009; 284: 18583-18587.

  • 36.

    Finn PF, Mesires NT, Vine M, Dice JF. Effects of small molecules on chaperone-mediated autophagy. Autophagy 2005; 1: 141-145.

  • 37.

    Khaleghian A, Ghaffari SH, Ahmadian S, Alimoghaddam K, Ghavamzadeh A. Metabolism of arsenic trioxide in acute promyelocytic leukemia cells. J Cell Biochem 2014; 115: 1729-1739.

  • 38.

    Hassani S, Khaleghian A, Ahmadian S, Alizadeh S, Alimoghaddam K, Ghavamzadeh A, Ghaffari SH. Redistribution of cell cycle by arsenic trioxide is associated with demethylation and expression changes of cell cycle related genes in acute promyelocytic leukemia cell line (NB4). Ann Hematol 2018; 97: 83-93.