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Article

The role of aldehyde dehydrogenase 1A1 in B-cell non-Hodgkin's lymphoma

  • Authors:
    • Ying-Hui Song
    • Mei-Zuo Zhong
    • Qin Chai
    • Kui-Yu Gong
    • Xiao-Lang Tan
    • Jin-Yue Hu
    • Gui-Hua Wang
  • View Affiliations / Copyright

    Affiliations: Department of Oncology, Changsha Central Hospital, Hunan 410004, P.R. China, Department of Oncology, Xiangya Hospital, Central South University, Changsha, P.R. China, Central Laboratory, Changsha Central Hospital, Changsha, P.R. China
  • Pages: 1261-1268
    |
    Published online on: January 18, 2018
       https://doi.org/10.3892/or.2018.6220
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Abstract

Previously we showed that aldehyde dehydrogenase 1A1 (ALDH1A1) is a new mediator for resistance of DLBCL to CHOP and a facility predictor of clinical prognosis. In the present study, knockdown and inhibitor of ALDH1A1 were applied to identify the role of ALDH1A1 in Raji cells. CCK-8 and clone formation assay were applied to determine the CHOP sensitivity and clone formation ability. Caspase colorimetric assay and Annexin V/FITC staining was performed to determine the degree of apoptosis. Western blot analysis was used to detect the NF-κB/STAT3 signaling proteins and apoptotic-associated proteins. Real-time quantitative PCR (RT-PCR) was used to identify the differential expression of ALDH1A1 between NHL patients and healthy donors. We demonstrated that inhibition of ALDH1A1 increased the sensitivity of Raji cells to CHOP, as indicated by increased cytotoxicity, reduced clonogenicity, activated caspase-3/-9, decreased NF-κB/STAT3 signaling and increased pro-apoptosis signaling, ad increased apoptosis rate. Moreover, we found high ALDH1A1 expression was associated with poor prognosis in NHL patients. Our data revealed the critical role of ALDH1A1 in NHL and provides a theoretical basis for the use of ALDH1A1 inhibitors in NHL patients.
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1 

Chiu BC and Weisenburger DD: An update of the epidemiology of non-Hodgkin's lymphoma. Clin Lymphoma. 4:161–168. 2003. View Article : Google Scholar : PubMed/NCBI

2 

Advani A, Coiffier B, Czuczman MS, Dreyling M, Foran J, Gine E, Gisselbrecht C, Ketterer N, Nasta S, Rohatiner A, et al: Safety, pharmacokinetics, and preliminary clinical activity of inotuzumab ozogamicin, a novel immunoconjugate for the treatment of B-cell non-Hodgkin's lymphoma: Results of a phase I study. J Clin Oncol. 28:2085–2093. 2010. View Article : Google Scholar : PubMed/NCBI

3 

Maxwell SA and Mousavi-Fard S: Non-Hodgkin's B-cell lymphoma: Advances in molecular strategies targeting drug resistance. Exp Biol Med. 238:971–990. 2013. View Article : Google Scholar

4 

Huang X, Meng B, Iqbal J, Ding BB, Perry AM, Cao W, Smith LM, Bi C, Jiang C, Greiner TC, et al: Activation of the STAT3 signaling pathway is associated with poor survival in diffuse large B-cell lymphoma treated with R-CHOP. J Clin Oncol. 31:4520–4528. 2013. View Article : Google Scholar : PubMed/NCBI

5 

Bohers E, Mareschal S, Bouzelfen A, Marchand V, Ruminy P, Maingonnat C, Ménard AL, Etancelin P, Bertrand P, Dubois S, et al: Targetable activating mutations are very frequent in GCB and ABC diffuse large B-cell lymphoma. Genes Chromosomes Cancer. 53:144–153. 2014. View Article : Google Scholar : PubMed/NCBI

6 

Duong HQ, Hwang JS, Kim HJ, Kang HJ, Seong YS and Bae I: Aldehyde dehydrogenase 1A1 confers intrinsic and acquired resistance to gemcitabine in human pancreatic adenocarcinoma MIA PaCa-2 cells. Int J Oncol. 41:855–861. 2012. View Article : Google Scholar : PubMed/NCBI

7 

Schäfer A, Teufel J, Ringel F, Bettstetter M, Hoepner I, Rasper M, Gempt J, Koeritzer J, Schmidt-Graf F, Meyer B, et al: Aldehyde dehydrogenase 1A1-a new mediator of resistance to temozolomide in glioblastoma. Neuro Oncol. 14:1452–1464. 2012. View Article : Google Scholar : PubMed/NCBI

8 

Shien K, Toyooka S, Yamamoto H, Soh J, Jida M, Thu KL, Hashida S, Maki Y, Ichihara E, Asano H, et al: Acquired resistance to EGFR inhibitors is associated with a manifestation of stem cell-like properties in cancer cells. Cancer Res. 73:3051–3061. 2013. View Article : Google Scholar : PubMed/NCBI

9 

Alamgeer M, Ganju V, Szczepny A, Russell PA, Prodanovic Z, Kumar B, Wainer Z, Brown T, Schneider-Kolsky M, Conron M, et al: The prognostic significance of aldehyde dehydrogenase 1A1 (ALDH1A1) and CD133 expression in early stage non-small cell lung cancer. Thorax. 68:1095–1104. 2013. View Article : Google Scholar : PubMed/NCBI

10 

de Beça FF, Caetano P, Gerhard R, Alvarenga CA, Gomes M, Paredes J and Schmitt F: Cancer stem cells markers CD44, CD24 and ALDH1 in breast cancer special histological types. J Clin Pathol. 66:187–191. 2013. View Article : Google Scholar : PubMed/NCBI

11 

Shen M, Bunaciu RP, Congleton J, Jensen HA, Sayam LG, Varner JD and Yen A: Interferon regulatory factor-1 binds c-Cbl, enhances mitogen activated protein kinase signalingand promotes retinoic acid-induced differentiation of HL-60 human myelo-monoblastic leukemia cells. Leuk Lymphoma. 52:2372–2379. 2011. View Article : Google Scholar : PubMed/NCBI

12 

Ikeda J, Mamat S, Tian T, Wang Y, Luo W, Rahadiani N, Aozasa K and Morii E: Reactive oxygen species and aldehyde dehydrogenase activity in Hodgkin lymphoma cells. Lab Invest. 92:606–614. 2012. View Article : Google Scholar : PubMed/NCBI

13 

Neradugomma NK, Subramaniam D, Tawfik OW, Goffin V, Kumar TR, Jensen RA and Anant S: Prolactin signaling enhances colon cancer stemness by modulating Notch signaling in a Jak2-STAT3/ERK manner. Carcinogenesis. 35:795–806. 2014. View Article : Google Scholar : PubMed/NCBI

14 

Liu L, Salnikov AV, Bauer N, Aleksandrowicz E, Labsch S, Nwaeburu C, Mattern J, Gladkich J, Schemmer P, Werner J and Herr I: Triptolide reverses hypoxia-induced epithelial-mesenchymal transition and stem-like features inpancreatic cancer by NF-κB downregulation. Int J Cancer. 134:2489–2503. 2014. View Article : Google Scholar : PubMed/NCBI

15 

Song YH, Zhong MZ, Gan PP, Yi PY, Tang YH, Liu YP, Jiang JQ and Li L: ALDH1A1 mediates resistance of diffuse large B cell lymphoma to the CHOP regimen. Tumour Biol. 35:11809–11817. 2014. View Article : Google Scholar : PubMed/NCBI

16 

Fujita S, Morii E, Rahadiani N, Wada N, Hori Y, Ikeda JI and Aozasa K: Significance of aldehyde dehydrogenase 1 expression in stromal cells of diffuse large B-cell lymphoma. Exp Ther Med. 2:591–594. 2011. View Article : Google Scholar : PubMed/NCBI

17 

Jiang J, Liu Y, Tang Y, Li L, Zeng R, Zeng S and Zhong M: ALDH1A1 induces resistance to CHOP in diffuse large B-cell lymphoma through activation of the JAK2/STAT3 pathway. Onco Targets Ther. 9:5349–5360. 2016. View Article : Google Scholar : PubMed/NCBI

18 

Wilson WH, Teruya-Feldstein J, Fest T, Harris C, Steinberg SM, Jaffe ES and Raffeld M: Relationship of p53, bcl-2, and tumor proliferation to clinical drug resistance in non-Hodgkin's lymphomas. Blood. 89:601–609. 1997.PubMed/NCBI

19 

Maxwell SA, Li Z, Jaye D, Ballard S, Ferrell J and Fu H: 14-3-3zeta mediates resistance of diffuse large B cell lymphoma to an anthracycline-based chemotherapeutic regimen. J Biol Chem. 284:22379–22389. 2009. View Article : Google Scholar : PubMed/NCBI

20 

Zhou Y, Wang Y, Ju X, Lan J, Zou H, Li S, Qi Y, Jia W, Hu J, Liang W, et al: Clinicopathological significance of ALDH1A1 in lung, colorectal, and breast cancers: A meta-analysis. Biomark Med. 9:777–790. 2015. View Article : Google Scholar : PubMed/NCBI

21 

Jones RJ, Gocke CD, Kasamon YL, Miller CB, Perkins B, Barber JP, Vala MS, Gerber JM, Gellert LL, Siedner M, et al: Circulating clonotypic B cells in classic Hodgkin lymphoma. Blood. 113:5920–5926. 2009. View Article : Google Scholar : PubMed/NCBI

22 

Ng SB, Ohshima K, Selvarajan V, Huang G, Choo SN, Miyoshi H, Shimizu N, Reghunathan R, Chua HC, Yeoh AE, et al: Epstein-Barr virus-associated T/natural killer-cell lymphoproliferative disorder in children and young adults has similar molecular signature to extranodal nasal natural killer/T-cell lymphoma but shows distinctive stem cell-like phenotype. Leuk Lymphoma. 56:2408–2415. 2015. View Article : Google Scholar : PubMed/NCBI

23 

Brennan SK, Meade B, Wang Q, Merchant AA, Kowalski J and Matsui W: Mantle cell lymphoma activation enhances bortezomib sensitivity. Blood. 116:4185–4191. 2010. View Article : Google Scholar : PubMed/NCBI

24 

Jiang L, Yu K, Du J, Ni W, Han Y, Gao S, Li H, Wu J, Zheng Y and Tan Y: Inhibition of p38 MAPK activity in B-NHL Raji cells by treatment with engineered CD20-specific T cells. Oncol Lett. 2:753–758. 2011. View Article : Google Scholar : PubMed/NCBI

25 

Pham LV, Tamayo AT, Yoshimura LC, Lo P, Terry N, Reid PS and Ford RJ: A CD40 Signalosome anchored in lipid rafts leads to constitutive activation of NF-kappaB andautonomous cell growth in B cell lymphomas. Immunity. 16:37–50. 2002. View Article : Google Scholar : PubMed/NCBI

26 

Zhang H, Chen Z, Miranda RN, Medeiros LJ and McCarty N: TG2 and NF-κB signaling coordinates the survival of mantle cell lymphoma cells via IL6-mediated autophagy. Cancer Res. 76:6410–6423. 2016. View Article : Google Scholar : PubMed/NCBI

27 

Ezell SA, Mayo M, Bihani T, Tepsuporn S, Wang S, Passino M, Grosskurth SE, Collins M, Parmentier J, Reimer C and Byth KF: Synergistic induction of apoptosis by combination of BTK and dual mTORC1/2 inhibitors in diffuse large B cell lymphoma. Oncotarget. 5:4990–5001. 2014. View Article : Google Scholar : PubMed/NCBI

28 

Koppaka V, Thompson DC, Chen Y, Ellermann M, Nicolaou KC, Juvonen RO, Petersen D, Deitrich RA, Hurley TD and Vasiliou V: Aldehyde dehydrogenase inhibitors: A comprehensive review of the pharmacology, mechanism of action, substrate specificity, and clinical application. Pharmacol Rev. 64:520–539. 2012. View Article : Google Scholar : PubMed/NCBI

29 

Lin J, Haffner MC, Zhang Y, Lee BH, Brennen WN, Britton J, Kachhap SK, Shim JS, Liu JO, Nelson WG, et al: Disulfiram is a DNA demethylating agent and inhibits prostate cancer cell growth. Prostate. 71:333–343. 2011. View Article : Google Scholar : PubMed/NCBI

30 

Kim JY, Cho Y, Oh E, Lee N, An H, Sung D, Cho TM and Seo JH: Disulfiram targets cancer stem-like properties and the HER2/Akt signaling pathway in HER2-positive breast cancer. Cancer Lett. 379:39–48. 2016. View Article : Google Scholar : PubMed/NCBI

31 

Liu X, Wang L, Cui W, Yuan X, Lin L, Cao Q, Wang N, Li Y, Guo W, Zhang X, et al: Targeting ALDH1A1 by disulfiram/copper complex inhibits non-small cell lung cancer recurrence driven by ALDH-positive cancer stem cells. Oncotarget. 7:58516–58530. 2016.PubMed/NCBI

32 

Paranjpe A, Zhang R, Ali-Osman F, Bobustuc GC and Srivenugopal KS: Disulfiram is a direct and potent inhibitor of human O6-methylguanine-DNA methyltransferase (MGMT) in brain tumor cells and mouse brain and markedly increases the alkylating DNA damage. Carcinogenesis. 35:692–702. 2014. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Song Y, Zhong M, Chai Q, Gong K, Tan X, Hu J and Wang G: The role of aldehyde dehydrogenase 1A1 in B-cell non-Hodgkin's lymphoma. Oncol Rep 39: 1261-1268, 2018.
APA
Song, Y., Zhong, M., Chai, Q., Gong, K., Tan, X., Hu, J., & Wang, G. (2018). The role of aldehyde dehydrogenase 1A1 in B-cell non-Hodgkin's lymphoma. Oncology Reports, 39, 1261-1268. https://doi.org/10.3892/or.2018.6220
MLA
Song, Y., Zhong, M., Chai, Q., Gong, K., Tan, X., Hu, J., Wang, G."The role of aldehyde dehydrogenase 1A1 in B-cell non-Hodgkin's lymphoma". Oncology Reports 39.3 (2018): 1261-1268.
Chicago
Song, Y., Zhong, M., Chai, Q., Gong, K., Tan, X., Hu, J., Wang, G."The role of aldehyde dehydrogenase 1A1 in B-cell non-Hodgkin's lymphoma". Oncology Reports 39, no. 3 (2018): 1261-1268. https://doi.org/10.3892/or.2018.6220
Copy and paste a formatted citation
x
Spandidos Publications style
Song Y, Zhong M, Chai Q, Gong K, Tan X, Hu J and Wang G: The role of aldehyde dehydrogenase 1A1 in B-cell non-Hodgkin's lymphoma. Oncol Rep 39: 1261-1268, 2018.
APA
Song, Y., Zhong, M., Chai, Q., Gong, K., Tan, X., Hu, J., & Wang, G. (2018). The role of aldehyde dehydrogenase 1A1 in B-cell non-Hodgkin's lymphoma. Oncology Reports, 39, 1261-1268. https://doi.org/10.3892/or.2018.6220
MLA
Song, Y., Zhong, M., Chai, Q., Gong, K., Tan, X., Hu, J., Wang, G."The role of aldehyde dehydrogenase 1A1 in B-cell non-Hodgkin's lymphoma". Oncology Reports 39.3 (2018): 1261-1268.
Chicago
Song, Y., Zhong, M., Chai, Q., Gong, K., Tan, X., Hu, J., Wang, G."The role of aldehyde dehydrogenase 1A1 in B-cell non-Hodgkin's lymphoma". Oncology Reports 39, no. 3 (2018): 1261-1268. https://doi.org/10.3892/or.2018.6220
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