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
Oncology Letters
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-1074 Online ISSN: 1792-1082
Journal Cover
April-2018 Volume 15 Issue 4

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
April-2018 Volume 15 Issue 4

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
Article Open Access

Effects of Clostridium difficile toxin A on K562/A02 cell proliferation, apoptosis and multi-drug resistance

  • Authors:
    • Yaming Xi
    • Zhuanzhen Ma
    • Hao Zhang
    • Maowen Yuan
    • Lina Wang
  • View Affiliations / Copyright

    Affiliations: Department of Hematology, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China
    Copyright: © Xi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 4215-4220
    |
    Published online on: February 1, 2018
       https://doi.org/10.3892/ol.2018.7921
  • 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

The aim of the present study was to investigate the cytotoxic effect and multi-drug resistance (MDR) of Clostridium difficile toxin A (TcdA) on K562/A02 cells, and understand its underlying molecular pathways. K562/A02 cells were treated with TcdA at different concentrations for 24, 48 and 72 h, and the inhibition effect and drug resistance of TcdA on K562/A02 cell proliferation was assessed by methyl thiazolyl tetrazolium colorimetric assay. Furthermore, cell cycle‑apoptosis was analyzed by flow cytometry, P‑glycoprotein (P‑gp) expression was determined by western blot analysis and caspase‑3 activity was measured using a caspase‑3 activity kit. TcdA inhibited K562/A02 cell proliferation in a time‑ and dose‑dependent manner. The inhibition rate of K562/A02 cells reached 8.76±0.76, 28.55±0.43, 47.89±0.27, 58.08±0.06 and 57.70±0.79% following treatment with 50, 100, 200, 400 and 800 ng/ml TcdA, respectively, for 24 h. K562/A02 cells in the G0/G1 phase increased and cells in the S phase decreased following treatment with TcdA (P<0.05), and the apoptotic rates in the 200 and 400 ng/ml concentration groups were 14.05 and 22.89%, respectively. In addition, TcdA (50 ng/ml) significantly inhibited the proliferation of K562/A02 cells and reduced the half maximal inhibitory concentration of these drugs in combination with chemotherapy drugs. The reversal folds were 3.09, 2.89 and 2.79, respectively. Furthermore, TcdA treatment was associated with the upregulation of P‑gp in K562/A02 cells, and caspase-3 activity was observed to increase in K562/A02 cells following TcdA treatment, when compared with untreated controls (P<0.05). These findings suggested that TcdA may be able to inhibit K562/A02 cell growth, induce cell apoptosis by decreasing P‑gp levels and caspase‑3 activation, and partially reverse MDR. Further studies are required to evaluate the potential of TcdA as a candidate for the chemotherapy of hematologic malignancies.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Aberuyi N, Rahgozar S and Moafi A: The role of ATP-binding cassette transporter A2 in childhood acute lymphoblastic leukemia multidrug resistance. Iran J Ped Hematol Oncol. 4:118–126. 2014.PubMed/NCBI

2 

Gillet JP and Gottesman MM: Mechanisms of multidrug resistance in cancer. Methods Mol Biol. 596:47–76. 2010. View Article : Google Scholar : PubMed/NCBI

3 

Valera ET, Scrideli CA, Queiroz RG, Mori BM and Tone LG: Multiple drug resistance protein (MDR-1), multidrug resistance-related protein (MRP) and lung resistance protein (LRP) gene expression in childhood acute lymphoblastic leukemia. Sao Paulo Med J. 122:166–171. 2004. View Article : Google Scholar : PubMed/NCBI

4 

Toyoda Y, Hagiya Y, Adachi T, Hoshijima K, Kuo MT and Ishikawa T: MRP class of human ATP binding cassette (ABC) transporters: Historical background and new research directions. Xenobiotica. 38:833–862. 2008. View Article : Google Scholar : PubMed/NCBI

5 

Peng Z, Xiao Z, Wang Y, Liu P, Cai Y, Lu S, Feng W and Han ZC: Reversal of P-glycoprotein-mediated multidrug resistance with small interference RNA (siRNA) in leukemia cells. Cancer Gene Ther. 11:707–712. 2004. View Article : Google Scholar : PubMed/NCBI

6 

Plasschaert SL, de Bont ES, Boezen M, vander Kolk DM, Daenen SM, Faber KN, Kamps WA, de Vries EG and Vellenga E: Expression of multidrug resistance-associated proteins predicts prognosis in childhood and adult acute lymphoblastic leukemia. Clin Cancer Res. 11:8661–8668. 2005. View Article : Google Scholar : PubMed/NCBI

7 

Swerts K, De Moerloose B, Dhooge C, Laureys G, Benoit Y and Philippe J: Prognostic significance of multidrug resistance-related proteins in childhood acute lymphoblastic leukaemia. Eur J Cancer. 42:295–309. 2006. View Article : Google Scholar : PubMed/NCBI

8 

Lyerly DM, Lockwood DE, Richardson SH and Wilkins TD: Biological activities of toxins A and B of Clostridium difficile. Infect Immun. 35:1147–1150. 1982.PubMed/NCBI

9 

Kamiya S, Reed PJ and Borriello SP: Purification and characterisation of Clostridium difficile toxin A by bovine thyroglobulin affinity chromatography and dissociation in denaturing conditions with or without reduction. J Med Microbiol. 30:69–77. 1989. View Article : Google Scholar : PubMed/NCBI

10 

Brito GA, Carneiro-Filho B, Orià RB, Destura RV, Lima AA and Guerrant RL: Clostridium difficile toxin A induces intestinal epithelial cell apoptosis and damage: Role of Gln and Ala-Gln in toxin A effects. Dig Dis Sci. 50:1271–1278. 2005. View Article : Google Scholar : PubMed/NCBI

11 

Nottrott S, Schoentaube J, Genth H, Just I and Gerhard R: Clostridium difficile toxin A-induced apoptosis is p53-independent but depends on glucosylation of Rho GTPases. Apoptosis. 12:1443–1453. 2007. View Article : Google Scholar : PubMed/NCBI

12 

Mahida YR, Makh S, Hyde S, Gray T and Borriello SP: Effect of Clostridium difficile toxin A on human intestinal epithelial cells: Induction of interleukin 8 production and apoptosis after cell detachment. Gut. 38:337–347. 1996. View Article : Google Scholar : PubMed/NCBI

13 

Brito GA, Fujji J, Carneiro-Filho BA, Lima AA, Obrig T and Guerrant RL: Mechanism of Clostridium difficile toxin A-induced apoptosis in T84 cells. J Infect Dis. 186:1438–1447. 2002. View Article : Google Scholar : PubMed/NCBI

14 

Carneiro BA, Fujii J, Brito GA, Alcantara C, Orià RB, Lima AA, Obrig T and Guerrant RL: Caspase and bid involvement in Clostridium difficile toxin A-induced apoptosis and modulation of toxin A effects by glutamine and alanyl-glutamine in vivo and in vitro. Infect Immun. 74:81–87. 2006. View Article : Google Scholar : PubMed/NCBI

15 

Meng XQ, Kamiya S, Yamakawa K, Ogura H and Nakamura S: Purification and characterisation of intracellular toxin A of Clostridium difficile. J Med Microbiol. 38:69–73. 1993. View Article : Google Scholar : PubMed/NCBI

16 

Meng QQ, Chen BA, Wu W, Shao ZY, Gao F and Zhao HH: Antitumor effects of low-frequency ultrasound combined with adriamycin on human leukemia multidrug resistance cell line K562/A02. Ai Zheng. 27:1182–1185. 2008.(In Chinese). PubMed/NCBI

17 

D'Auria KM, Kolling GL, Donato GM, Warren CA, Gray MC, Hewlett EL and Papin JA: In vivo physiological and transcriptional profiling reveals host responses to Clostridium difficile toxin A and toxin B. Infect Immun. 81:3814–3824. 2013. View Article : Google Scholar : PubMed/NCBI

18 

Wu D, Joyee AG, Nandagopal S, Lopez M, Ma X, Berry J and Lin F: Effects of Clostridium difficile toxin A and B on human T lymphocyte migration. Toxins. 5:926–938. 2013. View Article : Google Scholar : PubMed/NCBI

19 

Torres K and Horwitz SB: Mechanisms of Taxol-induced cell death are concentration dependent. Cancer Res. 58:3620–3626. 1998.PubMed/NCBI

20 

Murray AW: Recycling the cell cycle: Cyclins revisited. Cell. 116:221–234. 2004. View Article : Google Scholar : PubMed/NCBI

21 

Thompson CB: Apoptosis in the pathogenesis and treatment of disease. Science. 267:1456–1462. 1995. View Article : Google Scholar : PubMed/NCBI

22 

Pietenpol JA and Stewart ZA: Cell cycle checkpoint signaling: Cell cycle arrest versus apoptosis. Toxicology. 182:475–481. 2002. View Article : Google Scholar

23 

Zu Y, Yang Z, Tang S, Han Y and Ma J: Effects of P-glycoprotein and its inhibitors on apoptosis in K562 cells. Molecules. 19:13061–13075. 2014. View Article : Google Scholar : PubMed/NCBI

24 

Gibalova L, Seres M, Rusnak A, Ditte P, Labudova M, Uhrik B, Pastorek J, Sedlak J, Breier A and Sulova Z: P-glycoprotein depresses cisplatin sensitivity in L1210 cells by inhibiting cisplatin-induced caspase-3 activation. Toxicol In Vitro. 26:435–444. 2012. View Article : Google Scholar : PubMed/NCBI

25 

Hoshi T, Sasano H, Kato K, Yabuki N, Ohara S, Konno R, Asaki S, Toyota T, Tateno H and Nagura H: Immunohistochemistry of Caspase3/CPP32 in human stomach and its correlation with cell proliferation and apoptosis. Anticancer Res. 18:4347–4353. 1998.PubMed/NCBI

26 

Qa'Dan M, Ramsey M, Daniel J, Spyres LM, Safiejko-Mroczka B, Ortiz-Leduc W and Ballard JD: Clostridium difficile toxin B activates dual caspase-dependent and caspase-independent apoptosis in intoxicated cells. Cell Microbiol. 4:425–434. 2002. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Xi Y, Ma Z, Zhang H, Yuan M and Wang L: Effects of Clostridium difficile toxin A on K562/A02 cell proliferation, apoptosis and multi-drug resistance. Oncol Lett 15: 4215-4220, 2018.
APA
Xi, Y., Ma, Z., Zhang, H., Yuan, M., & Wang, L. (2018). Effects of Clostridium difficile toxin A on K562/A02 cell proliferation, apoptosis and multi-drug resistance. Oncology Letters, 15, 4215-4220. https://doi.org/10.3892/ol.2018.7921
MLA
Xi, Y., Ma, Z., Zhang, H., Yuan, M., Wang, L."Effects of Clostridium difficile toxin A on K562/A02 cell proliferation, apoptosis and multi-drug resistance". Oncology Letters 15.4 (2018): 4215-4220.
Chicago
Xi, Y., Ma, Z., Zhang, H., Yuan, M., Wang, L."Effects of Clostridium difficile toxin A on K562/A02 cell proliferation, apoptosis and multi-drug resistance". Oncology Letters 15, no. 4 (2018): 4215-4220. https://doi.org/10.3892/ol.2018.7921
Copy and paste a formatted citation
x
Spandidos Publications style
Xi Y, Ma Z, Zhang H, Yuan M and Wang L: Effects of Clostridium difficile toxin A on K562/A02 cell proliferation, apoptosis and multi-drug resistance. Oncol Lett 15: 4215-4220, 2018.
APA
Xi, Y., Ma, Z., Zhang, H., Yuan, M., & Wang, L. (2018). Effects of Clostridium difficile toxin A on K562/A02 cell proliferation, apoptosis and multi-drug resistance. Oncology Letters, 15, 4215-4220. https://doi.org/10.3892/ol.2018.7921
MLA
Xi, Y., Ma, Z., Zhang, H., Yuan, M., Wang, L."Effects of Clostridium difficile toxin A on K562/A02 cell proliferation, apoptosis and multi-drug resistance". Oncology Letters 15.4 (2018): 4215-4220.
Chicago
Xi, Y., Ma, Z., Zhang, H., Yuan, M., Wang, L."Effects of Clostridium difficile toxin A on K562/A02 cell proliferation, apoptosis and multi-drug resistance". Oncology Letters 15, no. 4 (2018): 4215-4220. https://doi.org/10.3892/ol.2018.7921
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