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
Molecular and Clinical Oncology
Join Editorial Board Propose a Special Issue
Print ISSN: 2049-9450 Online ISSN: 2049-9469
Journal Cover
March-2016 Volume 4 Issue 3

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
March-2016 Volume 4 Issue 3

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

Sensitivity of ovarian cancer cells to acetaminophen reveals biological pathways that affect patient survival

  • Authors:
    • Stephen H. Bush
    • Sharon Tollin
    • Douglas C. Marchion
    • Yin Xiong
    • Forough Abbasi
    • Ingrid J. Ramirez
    • Nadim Bou Zgheib
    • Bernadette Boac
    • Patricia L. Judson
    • Hye Sook Chon
    • Robert M. Wenham
    • Sachin M. Apte
    • Christopher L. Cubitt
    • Anders E. Berglund
    • Laura J. Havrilesky
    • Johnathan M. Lancaster
  • View Affiliations / Copyright

    Affiliations: Department of Women's Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA, Translational Research Core, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA, Cancer Informatics Core, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA, Duke University Medical Center, Durham, NC 27710, USA
  • Pages: 399-404
    |
    Published online on: January 7, 2016
       https://doi.org/10.3892/mco.2016.725
  • 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

Experimental and epidemiological data support the potential activity of acetaminophen against ovarian cancer (OVCA). In this study, we sought to confirm the activity of acetaminophen in OVCA cell lines and to investigate the molecular basis of response. A total of 16 OVCA cell lines underwent pretreatment (baseline) genome-wide expression measurements and were then treated with and analyzed for acetaminophen sensitivity. Pearson's correlation analysis was performed to identify genes that were associated with OVCA acetaminophen response. The identified genes were subjected to pathway analysis, and the expression of each represented pathway was summarized using principal component analysis. OVCA acetaminophen response pathways were analyzed in 4 external clinico‑genomic datasets from 820 women for associations with overall survival from OVCA. Acetaminophen exhibited antiproliferative activity against all tested OVCA cell lines, with half maximal inhibitory concentration values ranging from 63.2 to 403 µM. Pearson's correlation followed by biological pathway analysis identified 13 pathways to be associated with acetaminophen sensitivity (P<0.01). Associations were observed between patient survival from OVCA and expression of the following pathways: Development̸angiotensin signaling via β-arrestin (P=0.04), protein folding and maturation̸angiotensin system maturation (P=0.02), signal transduction̸c-Jun N-terminal kinase (JNK) pathway (P=0.03) and androstenedione and testosterone biosynthesis and metabolism (P=0.02). We confirmed that acetaminophen was active against OVCA cells in vitro. Furthermore, we identified 4 molecular signaling pathways associated with acetaminophen response that may also affect overall survival in women with OVCA, including the JNK pathway, which has been previously implicated in the mechanism of action of acetaminophen and is predictive of decreased survival in women with OVCA.
View Figures

Figure 1

Figure 2

View References

1 

Siegel R, Ma J, Zou Z and Jemal A: Cancer statistics, 2014. CA Cancer J Clin. 64:9–29. 2014. View Article : Google Scholar : PubMed/NCBI

2 

Ozols RF, Bundy BN, Greer BE, Fowler JM, Clarke-Pearson D, Burger RA, Mannel RS, DeGeest K, Hartenbach EM and Baergen R: Gynecologic Oncology Group: Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected stage III ovarian cancer: A Gynecologic Oncology Group study. J Clin Oncol. 21:3194–3200. 2003. View Article : Google Scholar : PubMed/NCBI

3 

McGuire WP, Hoskins WJ, Brady MF, Kucera PR, Partridge EE, Look KY, Clarke-Pearson DL and Davidson M: Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III and stage IV ovarian cancer. N Engl J Med. 334:1–6. 1996. View Article : Google Scholar : PubMed/NCBI

4 

Wu YJ, Neuwelt AJ, Muldoon LL and Neuwelt EA: Acetaminophen enhances cisplatin- and paclitaxel-mediated cytotoxicity to SKOV3 human ovarian carcinoma. Anticancer Res. 33:2391–2400. 2013.PubMed/NCBI

5 

Spooner JB and Harvey JG: The history and usage of paracetamol. J Int Med Res. 4(Suppl 4): 1–6. 1976.PubMed/NCBI

6 

Ameer B and Greenblatt DJ: Acetaminophen. Ann Int Med. 87:202–209. 1977. View Article : Google Scholar : PubMed/NCBI

7 

Botting RM: Mechanism of action of acetaminophen: Is there a cyclooxygenase 3? Clin Infect Dis. 31(Suppl 5): S202–S210. 2000. View Article : Google Scholar : PubMed/NCBI

8 

Moysich KB, Mettlin C, Piver MS, Natarajan N, Menezes RJ and Swede H: Regular use of analgesic drugs and ovarian cancer risk. Cancer Epidemiol Biomarkers Prev. 10:903–906. 2001.PubMed/NCBI

9 

Rodriguez-Burford C, Barnes MN, Oelschlager DK, Myers RB, Talley LI, Partridge EE and Grizzle WE: Effects of nonsteroidal anti-inflammatory agents (NSAIDs) on ovarian carcinoma cell lines: Preclinical evaluation of NSAIDs as chemopreventive agents. Clin Cancer Res. 8:202–209. 2002.PubMed/NCBI

10 

Cramer DW, Harlow BL, Titus-Ernstoff L, Bohlke K, Welch WR and Greenberg ER: Over-the-counter analgesics and risk of ovarian cancer. Lancet. 351:104–107. 1998. View Article : Google Scholar : PubMed/NCBI

11 

Baandrup L, Friis S, Dehlendorff C, Andersen KK, Olsen JH and Kjaer SK: Prescription use of paracetamol and risk for ovarian cancer in Denmark. J Natl Cancer Inst. 106:dju1112014. View Article : Google Scholar : PubMed/NCBI

12 

Lo-Ciganic WH, Zgibor JC, Bunker CH, Moysich KB, Edwards RP and Ness RB: Aspirin, nonaspirin nonsteroidal anti-inflammatory drugs, or acetaminophen and risk of ovarian cancer. Epidemiology. 23:311–319. 2012. View Article : Google Scholar : PubMed/NCBI

13 

Hannibal CG, Rossing MA, Wicklund KG and Cushing-Haugen KL: Analgesic drug use and risk of epithelial ovarian cancer. Am J Epidemiol. 167:1430–1437. 2008. View Article : Google Scholar : PubMed/NCBI

14 

Marchion DC, Cottrill HM, Xiong Y, Chen N, Bicaku E, Fulp WJ, Bansal N, Chon HS, Stickles XB, Kamath SG, et al: BAD phosphorylation determines ovarian cancer chemosensitivity and patient survival. Clin Cancer Res. 17:6356–6366. 2011. View Article : Google Scholar : PubMed/NCBI

15 

Chen DT, Nasir A, Culhane A, Venkataramu C, Fulp W, Rubio R, Wang T, Agrawal D, McCarthy SM, Gruidl M, et al: Proliferative genes dominate malignancy-risk gene signature in histologically-normal breast tissue. Breast Cancer Res Treatment. 119:335–346. 2010. View Article : Google Scholar

16 

Tothill RW, Tinker AV, George J, Brown R, Fox SB, Lade S, Johnson DS, Trivett MK, Etemadmoghadam D, Locandro B, et al: Novel molecular subtypes of serous and endometrioid ovarian cancer linked to clinical outcome. Clin Cancer Res. 14:5198–5208. 2008. View Article : Google Scholar : PubMed/NCBI

17 

Win S, Than TA, Han D, Petrovic LM and Kaplowitz N: c-Jun N-terminal kinase (JNK)-dependent acute liver injury from acetaminophen or tumor necrosis factor (TNF) requires mitochondrial Sab protein expression in mice. J Biol Chem. 286:35071–35078. 2011. View Article : Google Scholar : PubMed/NCBI

18 

Johnson GL and Nakamura K: The c-jun kinase/stress-activated pathway: Regulation, function and role in human disease. Biochim Biophys Acta. 1773:1341–1348. 2007. View Article : Google Scholar : PubMed/NCBI

19 

Weston CR and Davis RJ: The JNK signal transduction pathway. Curr Opin Cell Biol. 19:142–149. 2007. View Article : Google Scholar : PubMed/NCBI

20 

Czaja MJ: Cell signaling in oxidative stress-induced liver injury. Semin Liver Dis. 27:378–389. 2007. View Article : Google Scholar : PubMed/NCBI

21 

Han D, Ybanez MD, Ahmadi S, Yeh K and Kaplowitz N: Redox regulation of tumor necrosis factor signaling. Antioxidants Redox Signal. 11:2245–2263. 2009. View Article : Google Scholar

22 

Gunawan BK, Liu ZX, Han D, Hanawa N, Gaarde WA and Kaplowitz N: c-Jun N-terminal kinase plays a major role in murine acetaminophen hepatotoxicity. Gastroenterology. 131:165–178. 2006. View Article : Google Scholar : PubMed/NCBI

23 

Shibata W, Maeda S, Hikiba Y, Yanai A, Sakamoto K, Nakagawa H, Ogura K, Karin M and Omata M: c-Jun NH2-terminal kinase 1 is a critical regulator for the development of gastric cancer in mice. Cancer Res. 68:5031–5039. 2008. View Article : Google Scholar : PubMed/NCBI

24 

Vivas-Mejia P, Benito JM, Fernandez A, Han HD, Mangala L, Rodriguez-Aguayo C, Chavez-Reyes A, Lin YG, Carey MS, Nick AM, et al: c-Jun-NH2-kinase-1 inhibition leads to antitumor activity in ovarian cancer. Clin Cancer Res. 16:184–194. 2010. View Article : Google Scholar : PubMed/NCBI

25 

Mansouri A, Ridgway LD, Korapati AL, Zhang Q, Tian L, Wang Y, Siddik ZH, Mills GB and Claret FX: Sustained activation of JNK/p38 MAPK pathways in response to cisplatin leads to Fas ligand induction and cell death in ovarian carcinoma cells. J Biol Chem. 278:19245–19256. 2003. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Bush SH, Tollin S, Marchion DC, Xiong Y, Abbasi F, Ramirez IJ, Zgheib NB, Boac B, Judson PL, Chon HS, Chon HS, et al: Sensitivity of ovarian cancer cells to acetaminophen reveals biological pathways that affect patient survival. Mol Clin Oncol 4: 399-404, 2016.
APA
Bush, S.H., Tollin, S., Marchion, D.C., Xiong, Y., Abbasi, F., Ramirez, I.J. ... Lancaster, J.M. (2016). Sensitivity of ovarian cancer cells to acetaminophen reveals biological pathways that affect patient survival. Molecular and Clinical Oncology, 4, 399-404. https://doi.org/10.3892/mco.2016.725
MLA
Bush, S. H., Tollin, S., Marchion, D. C., Xiong, Y., Abbasi, F., Ramirez, I. J., Zgheib, N. B., Boac, B., Judson, P. L., Chon, H. S., Wenham, R. M., Apte, S. M., Cubitt, C. L., Berglund, A. E., Havrilesky, L. J., Lancaster, J. M."Sensitivity of ovarian cancer cells to acetaminophen reveals biological pathways that affect patient survival". Molecular and Clinical Oncology 4.3 (2016): 399-404.
Chicago
Bush, S. H., Tollin, S., Marchion, D. C., Xiong, Y., Abbasi, F., Ramirez, I. J., Zgheib, N. B., Boac, B., Judson, P. L., Chon, H. S., Wenham, R. M., Apte, S. M., Cubitt, C. L., Berglund, A. E., Havrilesky, L. J., Lancaster, J. M."Sensitivity of ovarian cancer cells to acetaminophen reveals biological pathways that affect patient survival". Molecular and Clinical Oncology 4, no. 3 (2016): 399-404. https://doi.org/10.3892/mco.2016.725
Copy and paste a formatted citation
x
Spandidos Publications style
Bush SH, Tollin S, Marchion DC, Xiong Y, Abbasi F, Ramirez IJ, Zgheib NB, Boac B, Judson PL, Chon HS, Chon HS, et al: Sensitivity of ovarian cancer cells to acetaminophen reveals biological pathways that affect patient survival. Mol Clin Oncol 4: 399-404, 2016.
APA
Bush, S.H., Tollin, S., Marchion, D.C., Xiong, Y., Abbasi, F., Ramirez, I.J. ... Lancaster, J.M. (2016). Sensitivity of ovarian cancer cells to acetaminophen reveals biological pathways that affect patient survival. Molecular and Clinical Oncology, 4, 399-404. https://doi.org/10.3892/mco.2016.725
MLA
Bush, S. H., Tollin, S., Marchion, D. C., Xiong, Y., Abbasi, F., Ramirez, I. J., Zgheib, N. B., Boac, B., Judson, P. L., Chon, H. S., Wenham, R. M., Apte, S. M., Cubitt, C. L., Berglund, A. E., Havrilesky, L. J., Lancaster, J. M."Sensitivity of ovarian cancer cells to acetaminophen reveals biological pathways that affect patient survival". Molecular and Clinical Oncology 4.3 (2016): 399-404.
Chicago
Bush, S. H., Tollin, S., Marchion, D. C., Xiong, Y., Abbasi, F., Ramirez, I. J., Zgheib, N. B., Boac, B., Judson, P. L., Chon, H. S., Wenham, R. M., Apte, S. M., Cubitt, C. L., Berglund, A. E., Havrilesky, L. J., Lancaster, J. M."Sensitivity of ovarian cancer cells to acetaminophen reveals biological pathways that affect patient survival". Molecular and Clinical Oncology 4, no. 3 (2016): 399-404. https://doi.org/10.3892/mco.2016.725
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