Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Experimental and Therapeutic Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-0981 Online ISSN: 1792-1015
Journal Cover
July-2020 Volume 20 Issue 1

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
July-2020 Volume 20 Issue 1

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML

  • Supplementary Files
    • Supplementary_Data.pdf
Article

N,N‑diethylaminobenzaldehyde targets aldehyde dehydrogenase to eradicate human pancreatic cancer cells

  • Authors:
    • Wenwen Wang
    • Shiya Zheng
    • Haiju He
    • Hao Ge
    • Borhan R. Saeed
  • View Affiliations / Copyright

    Affiliations: Department of Oncology, The Affiliated Wuxi No. 2 People's Hospital of Nanjing Medical University, Wuxi, Jiangsu 214000, P.R. China, Department of Oncology, Zhongda Hospital, Medical School, Southeast University, Nanjing, Jiangsu 210009, P.R. China, Department of Medicine V, University of Heidelberg, D‑69120 Heidelberg, Germany, Department of Oncology, Liyang People's Hospital, Liyang, Jiangsu 213300, P.R. China
  • Pages: 662-670
    |
    Published online on: April 27, 2020
       https://doi.org/10.3892/etm.2020.8691
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Pancreatic cancer is a common cause of worldwide cancer-related mortality with a poor 5-year survival rate. Aldehyde dehydrogenase (ALDH) activity is a possible marker for malignant stem cells in solid organ systems, including the pancreas, and N,N‑diethylaminobenzaldehyde (DEAB) is able to inhibit ALDH activity. In the present study, the role of DEAB in the treatment of pancreatic cancer cells and the potential underlying mechanisms were investigated. The ALDH activities of pancreatic cancer cell lines treated with or without DEAB were analyzed by an ALDEFLUOR™ assay. The Cell Counting Kit‑8 and colony formation assays, and cell cycle analysis were used to evaluate the viability, colony‑forming ability and cell quiescence of cell lines under DEAB treatment, respectively. DEAB and/or gemcitabine‑induced cell apoptosis was assessed by flow cytometry. DEAB reduced ALDH activity and inhibited the proliferation, colony‑forming ability and cell quiescence of pancreatic cancer cell lines. Compared with respective controls, DEAB alone and the combination of gemcitabine and DEAB significantly decreased cell viability and increased cell apoptosis. Moreover, reverse transcription‑PCR and western blotting were used to measure the expressions of B cell lymphoma 2 (Bcl2) associated X protein (Bax) and Bcl2 mRNA and protein. The anti‑cancer effect of DEAB was associated with upregulation of Bax expression. Therefore, targeting ALDH with DEAB may be a potential therapeutic choice for pancreatic cancer, demonstrating a synergic effect with gemcitabine.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Kamisawa T, Wood LD, Itoi T and Takaori K: Pancreatic cancer. Lancet. 388:73–85. 2016.PubMed/NCBI View Article : Google Scholar

2 

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.PubMed/NCBI View Article : Google Scholar

3 

Clarke MF, Dick JE, Dirks PB, Eaves CJ, Jamieson CH, Jones DL, Visvader J, Weissman IL and Wahl GM: Cancer stem cells-perspectives on current status and future directions: AACR Workshop on cancer stem cells. Cancer Res. 66:9339–9344. 2006.PubMed/NCBI View Article : Google Scholar

4 

Ishiwata T, Matsuda Y, Yoshimura H, Sasaki N, Ishiwata S, Ishikawa N, Takubo K, Arai T and Aida J: Pancreatic cancer stem cells: Features and detection methods. Pathol Oncol Res. 24:797–805. 2018.PubMed/NCBI View Article : Google Scholar

5 

Kim SK, Kim H, Lee DH, Kim TS, Kim T, Chung C, Koh GY, Kim H and Lim DS: Reversing the intractable nature of pancreatic cancer by selectively targeting ALDH-high, therapy-resistant cancer cells. PLoS One. 8(e78130)2013.PubMed/NCBI View Article : Google Scholar

6 

Moreb JS: Aldehyde dehydrogenase as a marker for stem cells. Curr Stem Cell Res Ther. 3:237–246. 2008.PubMed/NCBI View Article : Google Scholar

7 

Lin L, Jou D, Wang Y, Ma H, Liu T, Fuchs J, Li PK, Lü J, Li C and Lin J: STAT3 as a potential therapeutic target in ALDH+ and CD44+/CD24+ stem cell-like pancreatic cancer cells. Int J Oncol. 49:2265–2274. 2016.PubMed/NCBI View Article : Google Scholar

8 

Ginestier C, Hur MH, Charafe-Jauffret E, Monville F, Dutcher J, Brown M, Jacquemier J, Viens P, Kleer CG, Liu S, et al: ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell. 1:555–567. 2007.PubMed/NCBI View Article : Google Scholar

9 

Huang EH, Hynes MJ, Zhang T, Ginestier C, Dontu G, Appelman H, Fields JZ, Wicha MS and Boman BM: Aldehyde dehydrogenase 1 is a marker for normal and malignant human colonic stem cells (SC) and tracks SC overpopulation during colon tumorigenesis. Cancer Res. 69:3382–3389. 2009.PubMed/NCBI View Article : Google Scholar

10 

Park JW, Jung KH, Lee JH, Moon SH, Cho YS and Lee KH: Inhibition of aldehyde dehydrogenase 1 enhances the cytotoxic effect of retinaldehyde on A549 cancer cells. Oncotarget. 8:99382–99393. 2017.PubMed/NCBI View Article : Google Scholar

11 

MacDonagh L, Gallagher MF, Ffrench B, Gasch C, Breen E, Gray SG, Nicholson S, Leonard N, Ryan R, Young V, et al: Targeting the cancer stem cell marker, aldehyde dehydrogenase 1, to circumvent cisplatin resistance in NSCLC. Oncotarget. 8:72544–72563. 2017.PubMed/NCBI View Article : Google Scholar

12 

Landen CN Jr, Goodman B, Katre AA, Steg AD, Nick AM, Stone RL, Miller LD, Mejia PV, Jennings NB, Gershenson DM, et al: Targeting aldehyde dehydrogenase cancer stem cells in ovarian cancer. Mol Cancer Ther. 9:3186–3199. 2010.PubMed/NCBI View Article : Google Scholar

13 

Fleischman AG: ALDH marks leukemia stem cell. Blood. 119:3376–3377. 2012.PubMed/NCBI View Article : Google Scholar

14 

Morgan CA, Parajuli B, Buchman CD, Dria K and Hurley TD: N,N-diethylaminobenzaldehyde (DEAB) as a substrate and mechanism-based inhibitor for human ALDH isoenzymes. Chem Biol Interact. 234:18–28. 2015.PubMed/NCBI View Article : Google Scholar

15 

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.PubMed/NCBI View Article : Google Scholar

16 

Hoang VT, Hoffmann I, Borowski K, Zepeda-Moreno A, Ran D, Buss EC, Wuchter P, Eckstein V and Ho AD: Identification and separation of normal hematopoietic stem cells and leukemia stem cells from patients with acute myeloid leukemia. Methods Mol Biol. 1035:217–230. 2013.PubMed/NCBI View Article : Google Scholar

17 

Wang W, Bochtler T, Wuchter P, Manta L, He H, Eckstein V, Ho AD and Lutz C: Mesenchymal stromal cells contribute to quiescence of therapy-resistant leukemic cells in acute myeloid leukemia. Eur J Haematol. 99:392–398. 2017.PubMed/NCBI View Article : Google Scholar

18 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001.PubMed/NCBI View Article : Google Scholar

19 

Kallifatidis G, Labsch S, Rausch V, Mattern J, Gladkich J, Moldenhauer G, Büchler MW, Salnikov AV and Herr I: Sulforaphane increases drug-mediated cytotoxicity toward cancer stem-like cells of pancreas and prostate. Mol Ther. 19:188–195. 2011.PubMed/NCBI View Article : Google Scholar

20 

Kim MP, Fleming JB, Wang H, Abbruzzese JL, Choi W, Kopetz S, McConkey DJ, Evans DB and Gallick GE: ALDH activity selectively defines an enhanced tumor-initiating cell population relative to CD133 expression in human pancreatic adenocarcinoma. PLoS One. 6(e20636)2011.PubMed/NCBI View Article : Google Scholar

21 

Mueller MT, Hermann PC, Witthauer J, Rubio-Viqueira B, Leicht SF, Huber S, Ellwart JW, Mustafa M, Bartenstein P, D'Haese JG, et al: Combined targeted treatment to eliminate tumorigenic cancer stem cells in human pancreatic cancer. Gastroenterology. 137:1102–1113. 2009.PubMed/NCBI View Article : Google Scholar

22 

Jimeno A, Feldmann G, Suárez-Gauthier A, Rasheed Z, Solomon A, Zou GM, Rubio-Viqueira B, García-García E, López-Ríos F, Matsui W, et al: A direct pancreatic cancer xenograft model as a platform for cancer stem cell therapeutic development. Mol Cancer Ther. 8:310–314. 2009.PubMed/NCBI View Article : Google Scholar

23 

Kawamoto M, Umebayashi M, Tanaka H, Koya N, Nakagawa S, Kawabe K, Onishi H, Nakamura M and Morisaki T: Combined gemcitabine and metronidazole is a promising therapeutic strategy for cancer stem-like cholangiocarcinoma. Anticancer Res. 38:2739–2748. 2018.PubMed/NCBI View Article : Google Scholar

24 

Sawada O, Perusek L, Kohno H, Howell SJ, Maeda A, Matsuyama S and Maeda T: All-trans-retinal induces Bax activation via DNA damage to mediate retinal cell apoptosis. Exp Eye Res. 123:27–36. 2014.PubMed/NCBI View Article : Google Scholar

25 

Jin Z and El-Deiry WS: Overview of cell death signaling pathways. Cancer Biol Ther. 4:139–163. 2005.PubMed/NCBI View Article : Google Scholar

26 

Adams JM and Cory S: The Bcl-2 protein family: Arbiters of cell survival. Science. 281:1322–1326. 1998.PubMed/NCBI View Article : Google Scholar

27 

Meng E, Mitra A, Tripathi K, Finan MA, Scalici J, McClellan S, Madeira da Silva L, Reed E, Shevde LA, Palle K and Rocconi RP: ALDH1A1 maintains ovarian cancer stem cell-like properties by altered regulation of cell cycle checkpoint and DNA repair network signaling. PLoS One. 9(e107142)2014.PubMed/NCBI View Article : Google Scholar

28 

Canuto RA, Muzio G, Salvo RA, Maggiora M, Trombetta A, Chantepie J, Fournet G, Reichert U and Quash G: The effect of a novel irreversible inhibitor of aldehyde dehydrogenases 1 and 3 on tumour cell growth and death. Chem Biol Interact. 130-132:209–218. 2001.PubMed/NCBI View Article : Google Scholar

29 

Igney FH and Krammer PH: Death and anti-death: Tumour resistance to apoptosis. Nat Rev Cancer. 2:277–288. 2002.PubMed/NCBI View Article : Google Scholar

30 

Won M, Luo Y, Lee DH, Shin E, Suh DS, Kim TH, Jin H and Bae J: BAX is an essential key mediator of AP5M1-induced apoptosis in cervical carcinoma cells. Biochem Biophys Res Commun. 518:368–373. 2019.PubMed/NCBI View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Wang W, Zheng S, He H, Ge H and Saeed BR: N,N‑diethylaminobenzaldehyde targets aldehyde dehydrogenase to eradicate human pancreatic cancer cells. Exp Ther Med 20: 662-670, 2020.
APA
Wang, W., Zheng, S., He, H., Ge, H., & Saeed, B.R. (2020). N,N‑diethylaminobenzaldehyde targets aldehyde dehydrogenase to eradicate human pancreatic cancer cells. Experimental and Therapeutic Medicine, 20, 662-670. https://doi.org/10.3892/etm.2020.8691
MLA
Wang, W., Zheng, S., He, H., Ge, H., Saeed, B. R."N,N‑diethylaminobenzaldehyde targets aldehyde dehydrogenase to eradicate human pancreatic cancer cells". Experimental and Therapeutic Medicine 20.1 (2020): 662-670.
Chicago
Wang, W., Zheng, S., He, H., Ge, H., Saeed, B. R."N,N‑diethylaminobenzaldehyde targets aldehyde dehydrogenase to eradicate human pancreatic cancer cells". Experimental and Therapeutic Medicine 20, no. 1 (2020): 662-670. https://doi.org/10.3892/etm.2020.8691
Copy and paste a formatted citation
x
Spandidos Publications style
Wang W, Zheng S, He H, Ge H and Saeed BR: N,N‑diethylaminobenzaldehyde targets aldehyde dehydrogenase to eradicate human pancreatic cancer cells. Exp Ther Med 20: 662-670, 2020.
APA
Wang, W., Zheng, S., He, H., Ge, H., & Saeed, B.R. (2020). N,N‑diethylaminobenzaldehyde targets aldehyde dehydrogenase to eradicate human pancreatic cancer cells. Experimental and Therapeutic Medicine, 20, 662-670. https://doi.org/10.3892/etm.2020.8691
MLA
Wang, W., Zheng, S., He, H., Ge, H., Saeed, B. R."N,N‑diethylaminobenzaldehyde targets aldehyde dehydrogenase to eradicate human pancreatic cancer cells". Experimental and Therapeutic Medicine 20.1 (2020): 662-670.
Chicago
Wang, W., Zheng, S., He, H., Ge, H., Saeed, B. R."N,N‑diethylaminobenzaldehyde targets aldehyde dehydrogenase to eradicate human pancreatic cancer cells". Experimental and Therapeutic Medicine 20, no. 1 (2020): 662-670. https://doi.org/10.3892/etm.2020.8691
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team