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 Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1021-335X Online ISSN: 1791-2431
Journal Cover
April 2013 Volume 29 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 2013 Volume 29 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

Antitumor properties of salinomycin on cisplatin-resistant human ovarian cancer cells in vitro and in vivo: involvement of p38 MAPK activation

  • Authors:
    • Bei Zhang
    • Xueya Wang
    • Fengfeng Cai
    • Weijie Chen
    • Uli Loesch
    • Xiao Yan Zhong
  • View Affiliations / Copyright

    Affiliations: Laboratory for Gynecologic Oncology, Women's Hospital/Department of Biomedicine, University of Basel, CH-4031 Basel, Switzerland, Nanomedicine Research Group, Medical Intensive Care Unit, University Hospital Basel, CH-4031 Basel, Switzerland, Hospital Pharmacy, University Hospital Basel, CH-4031 Basel, Switzerland
  • Pages: 1371-1378
    |
    Published online on: January 17, 2013
       https://doi.org/10.3892/or.2013.2241
  • 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

In order to search for alternative agents to overcome chemoresistance during the treatment of ovarian cancer, this study aimed to examine the anticancer effects and action mechanism of salinomycin, a selective inhibitor of cancer stem cells, on cisplatin-resistant human ovarian cancer cell lines in vitro and in vivo. The concentration- (0.01-200 µM) and time‑dependent (24-72 h) growth inhibitory effects of salinomycin were observed in the ovarian cancer cell lines OV2008, C13, A2780, A2780-cp, SKOV3 and OVCAR3, by measuring cell viability using the resazurin reduction assay. The IC50 (24 h) range of salinomycin on the six cell lines was found to be 1.7-7.4 µM. After cisplatin-resistant C13 cells were treated with salinomycin, the percentage of apoptotic cells determined by flow cytometry was significantly increased, in a concentration- and time‑dependent manner. However, no cell cycle arrest was detected in the G1/G0, S and G2/M phases in the salinomycin‑treated and control cells. The Bio-Plex phosphoprotein 5-plex assay (Akt, IκB-α, ERK1/2, JNK and p38 MAPK) demonstrated a marked time- and concentration‑dependent increase in the phosphorylation of p38 MAPK, subsequent to salinomycin treatment. Moreover, salinomycin significantly suppressed tumor growth in a tumor xenograft model. These findings suggested that salinomycin efficiently inhibits the cisplatin-resistant human ovarian cancer cell line growth through the induction of apoptosis, potentially asso­ciated with the p38 MAPK activation.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Parkin DM, Bray F, Ferlay J and Pisani P: Global cancer statistics, 2002. CA Cancer J Clin. 55:74–108. 2005. View Article : Google Scholar

2 

Morrison J: Advances in the understanding and treatment of ovarian cancer. J Br Menopause Soc. 11:66–71. 2005. View Article : Google Scholar

3 

Munkarah A, Chatterjee M and Tainsky MA: Update on ovarian cancer screening. Curr Opin Obstet Gynecol. 19:22–26. 2007. View Article : Google Scholar

4 

McGuire WP III and Markman M: Primary ovarian cancer chemotherapy: current standards of care. Br J Cancer. 89(Suppl): S3–S8. 2003. View Article : Google Scholar : PubMed/NCBI

5 

Bristow RE and Chi DS: Platinum-based neoadjuvant chemotherapy and interval surgical cytoreduction for advanced ovarian cancer: a meta-analysis. Gynecol Oncol. 103:1070–1076. 2006. View Article : Google Scholar : PubMed/NCBI

6 

Cannistra SA: Cancer of the ovary. N Engl J Med. 351:2519–2529. 2004. View Article : Google Scholar : PubMed/NCBI

7 

Kelland LR: Emerging drugs for ovarian cancer. Expert Opin Emerg Drugs. 10:413–424. 2005. View Article : Google Scholar : PubMed/NCBI

8 

Harries M and Gore M: Part II: chemotherapy for epithelial ovarian cancer-treatment of recurrent disease. Lancet Oncol. 3:537–545. 2002. View Article : Google Scholar : PubMed/NCBI

9 

Harries M and Gore M: Part I: chemotherapy for epithelial ovarian cancer-treatment at first diagnosis. Lancet Oncol. 3:529–536. 2002. View Article : Google Scholar : PubMed/NCBI

10 

Jansen BA, Brouwer J and Reedijk J: Glutathione induces cellular resistance against cationic dinuclear platinum anticancer drugs. J Inorg Biochem. 89:197–202. 2002. View Article : Google Scholar : PubMed/NCBI

11 

Lee S, Choi EJ, Jin C and Kim DH: Activation of PI3K/Akt pathway by PTEN reduction and PIK3CA mRNA amplification contributes to cisplatin resistance in an ovarian cancer cell line. Gynecol Oncol. 97:26–34. 2005. View Article : Google Scholar : PubMed/NCBI

12 

Choi KC, Auersperg N and Leung PC: Mitogen-activated protein kinases in normal and (pre)neoplastic ovarian surface epithelium. Reprod Biol Endocrinol. 1:712003. View Article : Google Scholar : PubMed/NCBI

13 

Mabuchi S, Ohmichi M, Nishio Y, et al: Inhibition of NFkappaB increases the efficacy of cisplatin in in vitro and in vivo ovarian cancer models. J Biol Chem. 279:23477–23485. 2004. View Article : Google Scholar : PubMed/NCBI

14 

Rudin CM, Yang Z, Schumaker LM, et al: Inhibition of glutathione synthesis reverses Bcl-2-mediated cisplatin resistance. Cancer Res. 63:312–318. 2003.PubMed/NCBI

15 

Miyazaki Y, Shibuya M, Sugawara H, Kawaguchi O and Hirsoe C: Salinomycin, a new polyether antibiotic. J Antibiot. 27:814–821. 1974. View Article : Google Scholar : PubMed/NCBI

16 

Callaway TR, Edrington TS, Rychlik JL, et al: Ionophores: their use as ruminant growth promotants and impact on food safety. Curr Issues Intest Microbiol. 4:43–51. 2003.PubMed/NCBI

17 

Gupta PB, Onder TT, Jiang G, et al: Identification of selective inhibitors of cancer stem cells by high-throughput screening. Cell. 138:645–659. 2009. View Article : Google Scholar : PubMed/NCBI

18 

Fuchs D, Heinold A, Opelz G, Daniel V and Naujokat C: Salinomycin induces apoptosis and overcomes apoptosis resistance in human cancer cells. Biochem Biophys Res Commun. 390:743–749. 2009. View Article : Google Scholar : PubMed/NCBI

19 

Fuchs D, Daniel V, Sadeghi M, Opelz G and Naujokat C: Salinomycin overcomes ABC transporter-mediated multidrug and apoptosis resistance in human leukemia stem cell-like KG-1a cells. Biochem Biophys Res Commun. 394:1098–1104. 2010. View Article : Google Scholar : PubMed/NCBI

20 

Riccioni R, Dupuis ML, Bernabei M, et al: The cancer stem cell selective inhibitor salinomycin is a P-glycoprotein inhibitor. Blood Cells Mol Dis. 45:86–92. 2010. View Article : Google Scholar : PubMed/NCBI

21 

Lu D, Choi MY, Yu J, Castro JE, Kipps TJ and Carson DA: Salinomycin inhibits Wnt signaling and selectively induces apoptosis in chronic lymphocytic leukemia cells. Proc Natl Acad Sci USA. 108:13253–13257. 2011. View Article : Google Scholar : PubMed/NCBI

22 

Chang L and Karin M: Mammalian MAP kinase signalling cascades. Nature. 410:37–40. 2001. View Article : Google Scholar : PubMed/NCBI

23 

Chergui F, Chretien AS, Bouali S, et al: Validation of a phosphoprotein array assay for characterization of human tyrosine kinase receptor downstream signaling in breast cancer. Clin Chem. 55:1327–1336. 2009. View Article : Google Scholar : PubMed/NCBI

24 

Martin SJ and Green DR: Apoptosis and cancer: the failure of controls on cell death and cell survival. Crit Rev Oncol Hematol. 18:137–153. 1995. View Article : Google Scholar : PubMed/NCBI

25 

Reed JC: Apoptosis-targeted therapies for cancer. Cancer Cell. 3:17–22. 2003. View Article : Google Scholar

26 

Schwartz GK and Shah MA: Targeting the cell cycle: a new approach to cancer therapy. J Clin Oncol. 23:9408–9421. 2005. View Article : Google Scholar : PubMed/NCBI

27 

Vermeulen K, Van Bockstaele DR and Berneman ZN: The cell cycle: a review of regulation, deregulation and therapeutic targets in cancer. Cell Prolif. 36:131–149. 2003. View Article : Google Scholar : PubMed/NCBI

28 

Katso R, Okkenhaug K, Ahmadi K, White S, Timms J and Waterfield MD: Cellular function of phosphoinositide 3-kinases: implications for development, homeostasis, and cancer. Annu Rev Cell Dev Biol. 17:615–675. 2001. View Article : Google Scholar : PubMed/NCBI

29 

Fraser M, Leung BM, Yan X, Dan HC, Cheng JQ and Tsang BK: p53 is a determinant of X-linked inhibitor of apoptosis protein/Akt-mediated chemoresistance in human ovarian cancer cells. Cancer Res. 63:7081–7088. 2003.PubMed/NCBI

30 

Weir NM, Selvendiran K, Kutala VK, et al: Curcumin induces G2/M arrest and apoptosis in cisplatin-resistant human ovarian cancer cells by modulating Akt and p38 MAPK. Cancer Biol Ther. 6:178–184. 2007. View Article : Google Scholar : PubMed/NCBI

31 

Medema RH, Kops GJ, Bos JL and Burgering BM: AFX-like Forkhead transcription factors mediate cell-cycle regulation by Ras and PKB through p27kip1. Nature. 404:782–787. 2000. View Article : Google Scholar : PubMed/NCBI

32 

Hayden MS and Ghosh S: Shared principles in NF-kappaB signaling. Cell. 132:344–362. 2008. View Article : Google Scholar : PubMed/NCBI

33 

Aggarwal BB: Nuclear factor-kappaB: the enemy within. Cancer Cell. 6:203–208. 2004.PubMed/NCBI

34 

Ono K and Han J: The p38 signal transduction pathway: activation and function. Cell Signal. 12:1–13. 2000. View Article : Google Scholar

35 

Park SJ and Kim IS: The role of p38 MAPK activation in auranofin-induced apoptosis of human promyelocytic leukaemia HL-60 cells. Br J Pharmacol. 146:506–513. 2005. View Article : Google Scholar : PubMed/NCBI

36 

Wagner EF and Nebreda AR: Signal integration by JNK and p38 MAPK pathways in cancer development. Nat Rev Cancer. 9:537–549. 2009. View Article : Google Scholar : PubMed/NCBI

37 

Bulavin DV and Fornace AJ Jr: p38 MAP kinase's emerging role as a tumor suppressor. Adv Cancer Res. 92:95–118. 2004.

38 

Brozovic A, Fritz G, Christmann M, et al: Long-term activation of SAPK/JNK, p38 kinase and fas-L expression by cisplatin is attenuated in human carcinoma cells that acquired drug resistance. Int J Cancer. 112:974–985. 2004. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Zhang B, Wang X, Cai F, Chen W, Loesch U and Zhong XY: Antitumor properties of salinomycin on cisplatin-resistant human ovarian cancer cells in vitro and in vivo: involvement of p38 MAPK activation. Oncol Rep 29: 1371-1378, 2013.
APA
Zhang, B., Wang, X., Cai, F., Chen, W., Loesch, U., & Zhong, X.Y. (2013). Antitumor properties of salinomycin on cisplatin-resistant human ovarian cancer cells in vitro and in vivo: involvement of p38 MAPK activation. Oncology Reports, 29, 1371-1378. https://doi.org/10.3892/or.2013.2241
MLA
Zhang, B., Wang, X., Cai, F., Chen, W., Loesch, U., Zhong, X. Y."Antitumor properties of salinomycin on cisplatin-resistant human ovarian cancer cells in vitro and in vivo: involvement of p38 MAPK activation". Oncology Reports 29.4 (2013): 1371-1378.
Chicago
Zhang, B., Wang, X., Cai, F., Chen, W., Loesch, U., Zhong, X. Y."Antitumor properties of salinomycin on cisplatin-resistant human ovarian cancer cells in vitro and in vivo: involvement of p38 MAPK activation". Oncology Reports 29, no. 4 (2013): 1371-1378. https://doi.org/10.3892/or.2013.2241
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang B, Wang X, Cai F, Chen W, Loesch U and Zhong XY: Antitumor properties of salinomycin on cisplatin-resistant human ovarian cancer cells in vitro and in vivo: involvement of p38 MAPK activation. Oncol Rep 29: 1371-1378, 2013.
APA
Zhang, B., Wang, X., Cai, F., Chen, W., Loesch, U., & Zhong, X.Y. (2013). Antitumor properties of salinomycin on cisplatin-resistant human ovarian cancer cells in vitro and in vivo: involvement of p38 MAPK activation. Oncology Reports, 29, 1371-1378. https://doi.org/10.3892/or.2013.2241
MLA
Zhang, B., Wang, X., Cai, F., Chen, W., Loesch, U., Zhong, X. Y."Antitumor properties of salinomycin on cisplatin-resistant human ovarian cancer cells in vitro and in vivo: involvement of p38 MAPK activation". Oncology Reports 29.4 (2013): 1371-1378.
Chicago
Zhang, B., Wang, X., Cai, F., Chen, W., Loesch, U., Zhong, X. Y."Antitumor properties of salinomycin on cisplatin-resistant human ovarian cancer cells in vitro and in vivo: involvement of p38 MAPK activation". Oncology Reports 29, no. 4 (2013): 1371-1378. https://doi.org/10.3892/or.2013.2241
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