Arch Iran Med. 2018;21(6):251-259.
PMID: 29940744
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Original Article

7-Farnesyloxycoumarin Exerts Anti-cancer Effects on a Prostate Cancer Cell Line by 15-LOX-1 Inhibition

Saffiyeh Saboormaleki 1, Hamid Sadeghian 2, Ahmad Reza Bahrami 1,3, Ala Orafaie 1, Maryam M. Matin 1,3 *

1 Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran
2 Department of Laboratory Sciences, School of Paramedical Sciences, Mashhad University of Medical Sciences, Mashhad, Iran
3 Novel Diagnostics and Therapeutics Research Group, Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran
*Corresponding Author: Maryam M. Matin, PhD; Department of Biology and Institute of Biotechnology, Ferdowsi University of Mashhad, Park Square, Mashhad, Iran. Tel: +98-51-38805514, Fax: +98-51-38796416, Email: Email: matin@um.ac.ir

Abstract

Background: Prostate cancer is one of the leading causes of cancer related deaths in males worldwide. Overexpression of 15-lipoxygenase-1 (15-LOX-1) enzyme and high activity of its metabolic pathway is reported to be a driver for prostate cancer malignancy. Farnesyloxycoumarin derivatives (3f, 4f and 7f) inhibit lipoxygenase enzyme. We hypothesized that farnesyloxycoumarins may exert an anti-cancer effect on prostate cancer cells due to their 15-LOX-1 inhibitory potential.

Methods: The enzyme inhibitory activity of 3f, 4f and 7f was initially evaluated on PC-3 and DU145 prostate cancer cell lines. MTT assay was performed on cancer cell lines and HFF3 cell line to assess cytotoxicity of the compounds. The apoptotic morphology of cells after treatments was assessed by DAPI staining and single cell gel electrophoresis. Propidium iodide staining was also performed to detect cell cycle variations after treatment.

Results: 7f inhibited 15-LOX-1 at IC50=4.3 µg/mL, while 3f and 4f did not show high inhibitory activity. 7f reduced cell viability in PC-3 cells at IC50=22-31 µg/mL, however, no significant cytotoxicity was revealed on normal cells. DAPI staining and comet assay confirmed apoptosis and DNA damage in PC-3 cells after 7f treatment, while flow cytometry results revealed G1 arrest in PC-3 cells.

Conclusion: The results are indicative of a distinctive cytotoxic mechanism for 7f compared to other coumarins, possibly due to its 15-LOX-1 inhibitory potential. Thus, this compound is valued for further assessments with the aim of developing a promising targeted therapy for prostate cancer patients

Cite this article as: Saboormaleki S, Sadeghian H, Bahrami AR, Orafaie A, Matin MM. 7-Farnesyloxycoumarin exerts anti-cancer effects on a prostate cancer cell line by 15-LOX-1 inhibition. Arch Iran Med. 2018;21(6):251–259. 
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Submitted: 07 Jun 2017
Accepted: 25 Apr 2018
First published online: 01 Jun 2018
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