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

Publication ,  Journal Article
Bush, SH; Tollin, S; Marchion, DC; Xiong, Y; Abbasi, F; Ramirez, IJ; Zgheib, NB; Boac, B; Judson, PL; Chon, HS; Wenham, RM; Apte, SM ...
Published in: Mol Clin Oncol
March 2016

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: Development/angiotensin signaling via β-arrestin (P=0.04), protein folding and maturation/angiotensin system maturation (P=0.02), signal transduction/c-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.

Duke Scholars

Published In

Mol Clin Oncol

DOI

ISSN

2049-9450

Publication Date

March 2016

Volume

4

Issue

3

Start / End Page

399 / 404

Location

England

Related Subject Headings

  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis
  • 1004 Medical Biotechnology
  • 0601 Biochemistry and Cell Biology
 

Citation

APA
Chicago
ICMJE
MLA
NLM
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. Mol Clin Oncol, 4(3), 399–404. https://doi.org/10.3892/mco.2016.725
Bush, Stephen H., Sharon Tollin, Douglas C. Marchion, Yin Xiong, Forough Abbasi, Ingrid J. Ramirez, Nadim Bou Zgheib, et al. “Sensitivity of ovarian cancer cells to acetaminophen reveals biological pathways that affect patient survival.Mol Clin Oncol 4, no. 3 (March 2016): 399–404. https://doi.org/10.3892/mco.2016.725.
Bush SH, Tollin S, Marchion DC, Xiong Y, Abbasi F, Ramirez IJ, et al. Sensitivity of ovarian cancer cells to acetaminophen reveals biological pathways that affect patient survival. Mol Clin Oncol. 2016 Mar;4(3):399–404.
Bush, Stephen H., et al. “Sensitivity of ovarian cancer cells to acetaminophen reveals biological pathways that affect patient survival.Mol Clin Oncol, vol. 4, no. 3, Mar. 2016, pp. 399–404. Pubmed, doi:10.3892/mco.2016.725.
Bush SH, Tollin S, Marchion DC, Xiong Y, Abbasi F, Ramirez IJ, Zgheib NB, Boac B, Judson PL, Chon HS, Wenham RM, Apte SM, Cubitt CL, Berglund AE, Havrilesky LJ, Lancaster JM. Sensitivity of ovarian cancer cells to acetaminophen reveals biological pathways that affect patient survival. Mol Clin Oncol. 2016 Mar;4(3):399–404.

Published In

Mol Clin Oncol

DOI

ISSN

2049-9450

Publication Date

March 2016

Volume

4

Issue

3

Start / End Page

399 / 404

Location

England

Related Subject Headings

  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis
  • 1004 Medical Biotechnology
  • 0601 Biochemistry and Cell Biology