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Planta Med 2014; 80(05): 399-408
DOI: 10.1055/s-0034-1368183
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Matrine Cooperates with All-Trans Retinoic Acid on Differentiation Induction of All-Trans Retinoic Acid-Resistant Acute Promyelocytic Leukemia Cells (NB4-LR1): Possible Mechanisms

Dijiong Wu   *
1   Department of Hematology, Zhejiang Provincial Hospital of Traditional Chinese Medicine, Hangzhou, China
,
Keding Shao   *
1   Department of Hematology, Zhejiang Provincial Hospital of Traditional Chinese Medicine, Hangzhou, China
,
Jie Sun
2   Department of Bone Marrow Transplantation, First Affiliated Hospital of Zhejiang University, Hangzhou, China
,
Fuyun Zhu
3   Zhejiang University of Traditional Chinese Medicine, Hangzhou, China
,
Baodong Ye
1   Department of Hematology, Zhejiang Provincial Hospital of Traditional Chinese Medicine, Hangzhou, China
,
Tingting Liu
2   Department of Bone Marrow Transplantation, First Affiliated Hospital of Zhejiang University, Hangzhou, China
,
Yiping Shen
1   Department of Hematology, Zhejiang Provincial Hospital of Traditional Chinese Medicine, Hangzhou, China
,
He Huang
2   Department of Bone Marrow Transplantation, First Affiliated Hospital of Zhejiang University, Hangzhou, China
,
Yuhong Zhou
1   Department of Hematology, Zhejiang Provincial Hospital of Traditional Chinese Medicine, Hangzhou, China
› Author Affiliations
Further Information

Publication History

received 11 August 2013
revised 16 January 2014

accepted 29 January 2014

Publication Date:
11 March 2014 (online)

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Abstract

Retinoic acid resistance results in refractory disease, and recovery in acute promyelocytic leukemia remains a challenge in clinical practice, with no ideal chemotherapeutic drug currently available. Here we report on the effect of an active compound of Sophora flavescens called matrine (0.1 mmol/L) combined with all-trans retinoic acid (1 µmol/L) in alleviating retinoic acid resistance in acute promyelocytic leukemia-derived NB4-LR1 cells by differentiation induction, as can be seen by an induced morphology change, increased CD11b expression, and nitro blue tetrazolium reduction activity, and a decreased expression of the promyelocytic leukemia-retinoic acid receptor α fusion gene and protein product. We further explored the probable mechanism of how matrine promotes the recovery of differentiation ability in NB4-LR1 cells when exposed to all-trans retinoic acid. We observed that the combination of all-trans retinoic acid and matrine can increase the level of cyclic adenosine monophosphate and protein kinase A activity, reduce telomerase activity, and downregulate the protein expression of topoisomerase II beta in NB4-LR1 cells. The results of this study suggest the possible clinical utility of matrine in the treatment of retinoic acid-resistant acute promyelocytic leukemia.

Key words

matrine - retinoic acid-resistant - acute promyelocytic leukemia - all-trans retinoic acid - cellular differentiation - Sophora flavescens - Fabaceae

* Both of these authors contributed equally to this study.


Supporting Information

 

  • References

  • 1 Adès L, Guerci A, Raffoux E, Sanz M, Chevallier P, Lapusan S, Recher C, Thomas X, Rayon C, Castaigne S, Tournilhac O, de Botton S, Ifrah N, Cahn JY, Solary E, Gardin C, Fegeux N, Bordessoule D, Ferrant A, Meyer-Monard S, Vey N, Dombret H, Degos L, Chevret S, Fenaux P. European APL Group. Very long-term outcome of acute promyelocytic leukemia after treatment with all-trans retinoic acid and chemotherapy: the European APL Group experience. Blood 2010; 115: 1690-1696
    CrossrefPubMedGoogle Scholar
  • 2 Fenaux P, Wang ZZ, Degos L. Treatment of acute promyelocytic leukemia by retinoids. Curr Top Microbiol Immunol 2007; 313: 101-128
    PubMedGoogle Scholar
  • 3 Au WY, Kumana CR, Lee HK, Lin SY, Liu H, Yeung DY, Lau JS, Kwong YL. Oral arsenic trioxide-based maintenance regimens for first complete remission of acute promyelocytic leukemia: a 10-year follow-up study. Blood 2011; 118: 6535-6543
    CrossrefPubMedGoogle Scholar
  • 4 Long Y, Lin XT, Zeng KL, Zhang L. Efficacy of intramuscular matrine in the treatment of chronic hepatitis B. Hepatobiliary Pancreat Dis Int 2004; 3: 69-72
    PubMedGoogle Scholar
  • 5 Yang ZS, Chen JB, Zhang HB, Hu NN, Wang X. Therapeutic effect of matrine glucose injection combined with CHOP on non-Hodgkinʼs lymphoma. Chin Tradit Pat Med 2007; 29: 1728-1730
    PubMedGoogle Scholar
  • 6 Wu DJ, Shao KD, Sun J, Ye BD, Zhou YH. Clinical and experimental advance of matrine in the treatment of hematologic malignancies. J Clin Hematol (China) 2012; 25: 469-471
    PubMedGoogle Scholar
  • 7 Fang HY, Wu DJ, Shen YP. Efficacy of compound matrine injection combined with MPR in the treatment of Multiple Myeloma. Zhejiang JITCWM (China) 2012; 22: 109-111
    PubMedGoogle Scholar
  • 8 Zhang Y, Dong Z, Jin L, Zhang K, Zhao X, Fu J, Gong Y, Sun M, Yang B, Li B. Arsenic trioxide-induced hERG K(+) channel deficiency can be rescued by matrine and oxymatrine through up-regulating transcription factor Sp1 expression. Biochem Pharmacol 2013; 85: 59-68
    CrossrefPubMedGoogle Scholar
  • 9 Zhang S, Zhang Y, Zhuang Y, Wang J, Ye J, Zhang S, Wu J, Yu K, Han Y. Matrine induces apoptosis in human acute myeloid leukemia cells via the mitochondrial pathway and Akt inactivation. PLoS One 2012; 7: e46853
    CrossrefPubMedGoogle Scholar
  • 10 Zhang W, Dai BT, Xu YH. Effects of matrine on invasion and metastasis of leukemia cell line Jurkat. CJITWM (China) 2008; 28: 907-911
    PubMedGoogle Scholar
  • 11 Zhang LP, Jiang JK, Tam JW, Zhang Y, Liu XS, Xu XR, Liu BZ, He YJ. Effects of Matrine on proliferation and differentiation in K-562 cells. Leuk Res 2001; 25: 793-800
    CrossrefPubMedGoogle Scholar
  • 12 Wu DJ, Zhou YH, Zhu J, Zhao W, Zhong WJ, Wang Z, Qian H, Li R, Fu S, Sun J. Study on matrine alleviating retinoic acid resistance in acute promyelocytic leukemia. Chin J Hematol 2011; 32: 313-316
    PubMedGoogle Scholar
  • 13 Zhu Q, Yu Y, Jia PM, Cai X, Chen SJ, Chen Z, Wang ZY, Tong JH. In vitro study of the effects of arsenic trioxide combined with 8-CPT-cAMP on differentiation induction in retinoic acid resistant acute promyelocytic leukemia cells. Chin J Hematol 2003; 24: 6-9
    PubMedGoogle Scholar
  • 14 Hirashima K, Migita T, Sato S, Muramatsu Y, Ishikawa Y, Seimiya H. Telomere length influences cancer cell differentiation in vivo . Mol Cell Biol 2013; 33: 2988-2995
    CrossrefPubMedGoogle Scholar
  • 15 Georgopoulos NT, Kirkwood LA, Varley CL, MacLaine NJ, Aziz N, Southgate J. Immortalisation of normal human urothelial cells compromises differentiation capacity. Eur Urol 2011; 60: 141-149
    CrossrefPubMedGoogle Scholar
  • 16 He P, Liu Y, Zhang M, Wang X, Xi J, Wu D, Li J, Cao Y. Interferon-γ enhances promyelocytic leukemia protein expression in acute promyelocytic cells and cooperates with all-trans-retinoic acid to induce maturation of NB4 and NB4-LR1 cells. Exp Ther Med 2012; 3: 776-780
    PubMedGoogle Scholar
  • 17 Xu DR, Huang S, Long ZJ, Chen JJ, Zou ZZ, Li J, Lin DJ, Liu Q. Inhibition of mitotic kinase Aurora suppresses Akt-1 activation and induces apoptotic cell death in all-trans retinoid acid-resistant acute promyelocytic leukemia cells. J Transl Med 2011; 9: 74
    CrossrefPubMedGoogle Scholar
  • 18 Sato T, Okumura F, Iguchi A, Ariga T, Hatakeyama S. TRIM32 promotes retinoic acid receptor α-mediated differentiation in human promyelogenous leukemic cell line HL60. Biochem Biophys Res Commun 2012; 417: 594-600
    CrossrefPubMedGoogle Scholar
  • 19 Jing Y. The PML-RARalpha fusion protein and targeted therapy for acute promyelocytic leukemia. Leuk Lymphoma 2004; 45: 639-648
    CrossrefPubMedGoogle Scholar
  • 20 Zhao Q, Tao J, Zhu Q, Jia PM, Dou AX, Li X, Cheng F, Waxman S, Chen GQ, Chen SJ, Lanotte M, Chen Z, Tong JH. Rapid induction of cAMP/PKA pathway during retinoic acid-induced acute promyelocytic leukemia cell differentiation. Leukemia 2004; 18: 285-292
    CrossrefPubMedGoogle Scholar
  • 21 Jiao B, Ren ZH, Liu P, Chen LJ, Shi JY, Dong Y, Ablain J, Shi L, Gao L, Hu JP, Ren RB, de Thé H, Chen Z, Chen SJ. 8-CPT-cAMP/all-trans retinoic acid targets t(11; 17) acute promyelocytic leukemia through enhanced cell differentiation and PLZF/RARα degradation. Proc Natl Acad Sci U S A 2013; 110: 3495-3500
    CrossrefPubMedGoogle Scholar
  • 22 Asai M, Tsukamoto O, Minamino T, Asanuma H, Fujita M, Asano Y, Takahama H, Sasaki H, Higo S, Asakura M, Takashima S, Hori M, Kitakaze M. PKA rapidly enhances proteasome assembly and activity in in vivo canine hearts. J Mol Cell Cardiol 2009; 46: 452-462
    CrossrefPubMedGoogle Scholar
  • 23 Fang Y, Zhou X, Lin M, Jing H, Zhong L, Ying M, Luo P, Yang B, He Q. The ubiquitin-proteasome pathway plays essential roles in ATRA-induced leukemia cells G0/G1 phase arrest and transition into granulocytic differentiation. Cancer Biol Ther 2010; 10: 1157-1167
    CrossrefPubMedGoogle Scholar
  • 24 Gausdal G, Wergeland A, Skavland J, Nguyen E, Pendino F, Rouhee N, McCormack E, Herfindal L, Kleppe R, Havemann U, Schwede F, Bruserud O, Gjertsen BT, Lanotte M, Ségal-Bendirdjian E, Døskeland SO. Cyclic AMP can promote APL progression and protect myeloid leukemia cells against anthracycline-induced apoptosis. Cell Death Dis 2013; 4: e516
    CrossrefPubMedGoogle Scholar
  • 25 Yamada O, Ozaki K, Nakatake M, Kakiuchi Y, Akiyama M, Mitsuishi T, Kawauchi K, Matsuoka R. Akt and PKC are involved not only in upregulation of telomerase activity but also in cell differentiation-related function via mTORC2 in leukemia cells. Histochem Cell Biol 2010; 134: 555-563
    CrossrefPubMedGoogle Scholar
  • 26 Pendino F, Hillion J, Dudognon C, Delaunay J, Mourah S, Podgorniak MP, Lafon I, Chomienne C, Lanotte M, Dombret H, Rousselot P, Ségal-Bendirdjian E. Telomerase targeting by retinoids in cells from patients with myeloid leukemias of various subtypes, not only APL. Leukemia 2006; 20: 599-603
    CrossrefPubMedGoogle Scholar
  • 27 Akiyama M, Yamada O, Yanagisawa T, Fujisawa K, Eto Y, Yamada H. Analysis of telomerase activity and RNA expression in a patient with acute promyelocytic leukemia treated with all-trans retinoic acid. Pediatr Blood Cancer 2006; 46: 506-511
    CrossrefPubMedGoogle Scholar
  • 28 Pendino F, Sahraoui T, Lanotte M, Ségal-Bendirdjian E. A novel mechanism of retinoic acid resistance in acute promyelocytic leukemia cells through a defective pathway in telomerase regulation. Leukemia 2002; 16: 826-832
    CrossrefPubMedGoogle Scholar
  • 29 Sun J, Huang H, Zhu Y, Lan J, Li J, Lai X, Yu J. The expression of telomeric proteins and their probable regulation of telomerase during the differentiation of all-trans-retinoic acid-responsive and -resistant acute promyelocytic leukemia cells. Int J Hematol 2005; 82: 215-223
    CrossrefPubMedGoogle Scholar
  • 30 Zhu B, Zhang LH, Zhao YM, Cui JR, Strada SJ. 8-chloroadenosine induced HL-60 cell growth inhibition, differentiation, and G(0)/G(1) arrest involves attenuated cyclin D1 and telomerase and up-regulated p 21(WAF1/CIP1). J Cell Biochem 2006; 97: 166-177
    CrossrefPubMedGoogle Scholar
  • 31 Wang AP, Zang T, Zhu LL. Influences of 8-Br-cAMP on the telomerase activity and P53 expression in the human lung adenocarcinoma cell A549 line. J Zhengzhou Univ (Med Sci) 2002; 37: 469-471
    PubMedGoogle Scholar
  • 32 Vávrová A, Šimůnek T. DNA topoisomerase IIβ: a player in regulation of gene expression and cell differentiation. Int J Biochem Cell Biol 2012; 44: 834-837
    CrossrefPubMedGoogle Scholar
  • 33 McNamara S, Wang H, Hanna N, Miller jr. WH. Topoisomerase II beta negatively modulates retinoic acid receptor alpha function: a novel mechanism of retinoic acid resistance. Mol Cell Biol 2008; 28: 2066-2077
    CrossrefPubMedGoogle Scholar
  • 34 Yang SY, Jia XZ, Feng LY, Li SY, An GS, Ni JH, Jia HT. Inhibition of topoisomerase II by 8-chloro-adenosine triphosphate induces DNA double-stranded breaks in 8-chloro-adenosine-exposed human myelocytic leukemia K562 cells. Biochem Pharmacol 2009; 77: 433-443
    CrossrefPubMedGoogle Scholar
  • 35 Kroll DJ, Sullivan DM, Gutierrez-Hartmann A, Hoeffler JP. Modification of DNA topoisomerase II activity via direct interactions with the cyclic adenosine-3′,5′-monophosphate response element-binding protein and related transcription factors. Mol Endocrinol 1993; 7: 305-318
    PubMedGoogle Scholar