Tumor Biology

, Volume 37, Issue 7, pp 9959–9966 | Cite as

Curcumin analogue, A13, exhibits anti-leukemia effect via inhibiting STAT3

  • Qiaoyou Weng
  • Luqing Ren
  • Lu Guo
  • Yan Hu
  • Haixia Zhou
  • Yuyan Bao
  • Lingfeng Chen
  • Guang Liang
  • Yi Wang
  • Jichen Ruan
Original Article


Abnormal activation of signal transducer and activator of transcription 3 (STAT3) was reported in some leukemia, and inhibition of STAT3 can be the strategy for the leukemia treatment in clinic. In this study, we tested the anti-tumor effect of compound A13, a water-soluble analogue of curcumin, in vitro and in vivo. Herein, we show that A13 was able to reduce the viability of mastocytoma (P815 cells) and reticulum cell sarcoma (A20 cells) as measured by MTS assay. This effect was accompanied by a marked increase in the proportion of apoptotic cells as measured by flow cytometry. Furthermore, Western blot analysis suggested that the anti-leukemia effect of A13 was realized via STAT3 inhibition. In addition, systemic treatment with A13 in the A20-bearing mice for 60 days resulted in a significant improvement of survival rate and marked reduction of liver metastasis. In summary, our data show that the A13 treatment could effectively be applied to acute leukemia via inhibiting STAT3 signaling pathway.


Curcumin analogue Water-soluble Anti-leukemia STAT3 



The authors thank Professor Yong-Guang Yang from the Columbia Center for Translational Immunology, Columbia University Medical Center (New York, NY), for providing the A20 cell line, which was obtained from the American Type Culture Collection (ATCC).

This study was supported by the National Natural Science Funding of China (81102452 to Y.W.) and Natural Science Funding of Zhejiang (LQ16H160019 to Q.W.).

Compliance with ethical standards

Conflicts of interest



  1. 1.
    Thomas DA, Kantarjian H, Smith TL, Koller C, Cortes J, O’Brien S, et al. Primary refractory and relapsed adult acute lymphoblastic leukemia: characteristics, treatment results, and prognosis with salvage therapy. Cancer. 1999;86:1216–30.CrossRefPubMedGoogle Scholar
  2. 2.
    Zhao J, Xu Y, Zong Y, Zhang S, Song Y, Yu K, et al. Inhibition of stat3 expression induces apoptosis and suppresses proliferation in human leukemia hl-60 cells. Hematology. 2011;16:232–5.CrossRefPubMedGoogle Scholar
  3. 3.
    Benekli M, Baumann H, Wetzler M. Targeting signal transducer and activator of transcription signaling pathway in leukemias. J Clin Oncol. 2009;27:4422–32.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Mangolini M, de Boer J, Walf-Vorderwulbecke V, Pieters R, den Boer ML, Williams O. Stat3 mediates oncogenic addiction to tel-aml1 in t(12;21) acute lymphoblastic leukemia. Blood. 2013;122:542–9.CrossRefPubMedGoogle Scholar
  5. 5.
    Adamaki M, Tsotra M, Vlahopoulos S, Zampogiannis A, Papavassiliou AG, Moschovi M. STAT transcript levels in childhood acute lymphoblastic leukemia: STAT1 and STAT3 transcript correlations. Leuk Res. 2015;S0145-2126(15):30379–9.Google Scholar
  6. 6.
    Epling-Burnette PK, Liu JH, Catlett-Falcone R, Turkson J, Oshiro M, Kothapalli R, et al. Inhibition of STAT3 signaling leads to apoptosis of leukemic large granular lymphocytes and decreased Mcl-1 expression. J Clin Invest. 2001;107:351–62.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Bi L, Yu Z, Fau-Wu J, Fau-Yu K, Fau-Hong G, Fau-Lu Z, et al. Honokiol inhibits constitutive and inducible STAT3 signaling via PU.1-induced SHP1 expression in acute myeloid leukemia cells. Tohoku J Exp Med. 2015;237(3):163–72.CrossRefPubMedGoogle Scholar
  8. 8.
    Gong C, Deng S, Wu Q, Xiang M, Wei X, Li L, et al. Improving antiangiogenesis and anti-tumor activity of curcumin by biodegradable polymeric micelles. Biomaterials. 2013;34:1413–32.CrossRefPubMedGoogle Scholar
  9. 9.
    Nakmareong S, Kukongviriyapan U, Pakdeechote P, Donpunha W, Kukongviriyapan V, Kongyingyoes B, et al. Antioxidant and vascular protective effects of curcumin and tetrahydrocurcumin in rats with L-NAME-induced hypertension. Naunyn Schmiedeberg’s Arch Pharmacol. 2011;383:519–29.CrossRefGoogle Scholar
  10. 10.
    Sun D, Zhuang X, Xiang X, Liu Y, Zhang S, Liu C, et al. A novel nanoparticle drug delivery system: the anti-inflammatory activity of curcumin is enhanced when encapsulated in exosomes. Mol Ther. 2010;18:1606–14.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Fetoni AR, Paciello F, Mezzogori D, Rolesi R, Eramo SL, Paludetti G, et al. Molecular targets for anticancer redox chemotherapy and cisplatin-induced ototoxicity: the role of curcumin on pSTAT3 and Nrf-2 signalling. Br J Cancer. 2015;113:1434–44.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Pandey A, Vishnoi K, Mahata S, Tripathi SC, Misra SP, Misra V, et al. Berberine and curcumin target survivin and stat3 in gastric cancer cells and synergize actions of standard chemotherapeutic 5-fluorouracil. Nutr Cancer. 2015;67(8):1293–304. 1–12.CrossRefPubMedGoogle Scholar
  13. 13.
    Chung SS, Vadgama JV. Curcumin and epigallocatechin gallate inhibit the cancer stem cell phenotype via down-regulation of STAT3-NFkappaB signaling. Anticancer Res. 2015;35:39–46.PubMedPubMedCentralGoogle Scholar
  14. 14.
    Mahmood K, Zia KM, Zuber M, Salman M, Anjum MN. Recent developments in curcumin and curcumin based polymeric materials for biomedical applications: a review. Int J Biol Macromol. 2015;81:877–90.CrossRefPubMedGoogle Scholar
  15. 15.
    Liang G, Li X, Chen L, Yang S, Wu X, Studer E, et al. Synthesis and anti-inflammatory activities of mono-carbonyl analogues of curcumin. Bioorg Med Chem Lett. 2008;18:1525–9.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Liang G, Yang S, Zhou H, Shao L, Huang K, Xiao J, et al. Synthesis, crystal structure and anti-inflammatory properties of curcumin analogues. Eur J Med Chem. 2009;44:915–9.CrossRefPubMedGoogle Scholar
  17. 17.
    Liang G, Zhou H, Wang Y, Gurley EC, Feng B, Chen L, et al. Inhibition of LPS-induced production of inflammatory factors in the macrophages by mono-carbonyl analogues of curcumin. J Cell Mol Med. 2009;13:3370–9.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Wang Y, Yu C, Pan Y, Yang X, Huang Y, Feng Z, et al. A novel synthetic mono-carbonyl analogue of curcumin, A13, exhibits anti-inflammatory effects in vivo by inhibition of inflammatory mediators. Inflammation. 2012;35:594–604.CrossRefPubMedGoogle Scholar
  19. 19.
    Liang G, Yang S, Jiang L, Zhao Y, Shao L, Xiao J, et al. Synthesis and anti-bacterial properties of mono-carbonyl analogues of curcumin. Chem Pharm Bull. 2008;56:162–7.CrossRefPubMedGoogle Scholar
  20. 20.
    Gately S, Li WW. Multiple roles of COX-2 in tumor angiogenesis: a target for antiangiogenic therapy. Semin Oncol. 2004;31:2–11.CrossRefPubMedGoogle Scholar
  21. 21.
    Soslow RA, Dannenberg AJ, Rush D, Woerner BM, Khan KN, Masferrer J, et al. COX-2 is expressed in human pulmonary, colonic, and mammary tumors. Cancer. 2000;89:2637–45.CrossRefPubMedGoogle Scholar
  22. 22.
    Kunnumakkara AB, Nair AS, Sung B, Pandey MK, Aggarwal BB. Boswellic acid blocks signal transducers and activators of transcription 3 signaling, proliferation, and survival of multiple myeloma via the protein tyrosine phosphatase SHP-1. Mol Cancer Res. 2009;7:118–28.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Aggarwal BB, Kunnumakkara AB, Harikumar KB, Gupta SR, Tharakan ST, Koca C, et al. Signal transducer and activator of transcription-3, inflammation, and cancer: how intimate is the relationship? Ann N Y Acad Sci. 2009;1171:59–76.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Nam S, Xie J, Perkins A, Ma Y, Yang F, Wu J, et al. Novel synthetic derivatives of the natural product berbamine inhibit Jak2/Stat3 signaling and induce apoptosis of human melanoma cells. Mol Oncol. 2012;6:484–93.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  • Qiaoyou Weng
    • 1
    • 2
  • Luqing Ren
    • 1
  • Lu Guo
    • 1
  • Yan Hu
    • 1
  • Haixia Zhou
    • 3
  • Yuyan Bao
    • 1
  • Lingfeng Chen
    • 1
  • Guang Liang
    • 1
  • Yi Wang
    • 1
  • Jichen Ruan
    • 1
    • 3
  1. 1.Chemical Biology Research Center, School of Pharmaceutical SciencesWenzhou Medical UniversityWenzhouChina
  2. 2.Department of Interventional Radiology, the 5th Affiliated HospitalWenzhou Medical UniversityLishuiChina
  3. 3.Department of Pediatric Hematology Oncology, the 2nd Affiliated Hospital and Yuying Children’s HospitalWenzhou Medical UniversityWenzhouChina

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