Biomarkers of sensitivity to potent and selective antitumor 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole (5F203) in ovarian cancer
Article first published online: 15 AUG 2013
Copyright © 2013 Wiley Periodicals, Inc.
Journal of Cellular Biochemistry
Volume 114, Issue 10, pages 2392–2404, October 2013
How to Cite
Callero, M. A., Luzzani, G. A., De Dios, D. O., Bradshaw, T. D. and Loaiza Perez, A. I. (2013), Biomarkers of sensitivity to potent and selective antitumor 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole (5F203) in ovarian cancer. J. Cell. Biochem., 114: 2392–2404. doi: 10.1002/jcb.24589
- Issue published online: 15 AUG 2013
- Article first published online: 15 AUG 2013
- Accepted manuscript online: 20 MAY 2013 09:50AM EST
- Manuscript Accepted: 1 MAY 2013
- Manuscript Received: 7 MAR 2013
- Institute of Oncology Ángel H. Roffo, University of Buenos Aires, Argentina
- OVARIAN CANCER;
2-(4-Amino-3-methylphenyl)-5-fluorobenzothiazole (5F203, NSC 703786) lysylamide belongs to a novel mechanistic class of antitumor agents. It elicits activity against ovarian, breast, kidney and colorectal cancer models. In sensitive breast cancer cells, 5F203 activates aryl hydrocarbon receptor (AhR) signaling. Herein, we evaluate the role of AhR in 5F203 activity in two ovarian cancer cell lines: IGROV-1 (sensitive to 5F203), SKOV-3 (resistant to this agent). In addition, cancer cells have been isolated from ascites fluid of ovarian cancer patients; sensitivity to 5F203 and concurrent AhR signal transduction has been examined in ascites-isolated ovarian cancer patients' cells. 5F203 induced enhanced CYP1A1 expression, AhR translocation and ROS formation in IGROV-1 cells and ascites-isolated ovarian cancer cells that were sensitive to 5F203. In IGROV-1 cells 5F203-induced ROS formation was accompanied by JNK, ERK and P38MAPK phosphorylation, DNA damage and cell cycle arrest prior to apoptosis. In contrast, 5F203 failed to induce CYP1A1 expression, AhR translocation or oxidative stress in 5F203-resistant SKOV-3 cells, or in ovarian cancer ascites cells inherently resistant to this agent. We propose that AhR may represent a new molecular target in the treatment of ovarian tumors and 5F203 may exemplify a potential novel treatment. Furthermore, putative biomarkers of sensitivity to this agent have been identified. J. Cell. Biochem. 114: 2392–2404, 2013. © 2013 Wiley Periodicals, Inc.